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3.
Ann Palliat Med ; 9(5): 3373-3378, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33065788

RESUMO

BACKGROUND: The coronavirus disease (COVID-19) poses an unprecedented challenge to health and epidemic prevention system, especially the healthcare of patients with cancer. We sought to study the impact of COVID-19 on lung cancer patients in our center. METHODS: We initiated a retrospectively study to analyze the impact of COVID-19 on lung cancer patients in our center, who were accepted for routine anticancer treatment before the epidemic and planned to return to hospital in January and February of 2020. RESULTS: A total of 161 cases of lung cancer were included in the final analysis. As of April 15, 95 patients had delayed their return visit, and 47 cases were finally designated as having delayed admission during the epidemic and having to discontinue or delay their regular anticancer treatments. Of these 47 delayed patients, 33 were evaluated for tumor status using a computed tomography scan, 6 of these 33 cases (18.18%) were diagnosed as progressive disease (PD), and 5 cases did not return for visit. CONCLUSIONS: This is the first study investigating impact of COVID-19 on non-COVID-19 lung cancer patients during the pandemic. The study demonstrates the significant impact of the COVID-19 crisis on oncological care, indicating the need for appropriate change of treatment decisions and continued follow-up and psycho-oncological support during this pandemic.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Infecções por Coronavirus , Imunoterapia , Neoplasias Pulmonares/terapia , Pandemias , Pneumonia Viral , Radioterapia , Carcinoma de Pequenas Células do Pulmão/terapia , Tempo para o Tratamento/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Quimiorradioterapia , China , Assistência à Saúde , Progressão da Doença , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem
4.
Tumour Biol ; 42(9): 1010428320958603, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32964798

RESUMO

This study aimed to investigate whether changes in progastrin-releasing peptide (ProGRP) levels correlate with treatment response and can be used to optimize clinical management of patients with small-cell lung cancer. Patients with small-cell lung cancer (any stage) receiving chemotherapy were eligible. ProGRP was measured in serum/plasma at baseline and after each chemotherapy cycle using the Elecsys® ProGRP assay (Roche Diagnostics). Treatment response was assessed by computed tomography scan. The primary objective was to examine whether changes in ProGRP levels correlated with computed tomography scan results after two cycles of chemotherapy. The prognostic value of ProGRP among patients receiving first-line chemotherapy was also assessed. Overall, 261 patients from six centers were eligible. Among patients with elevated baseline ProGRP (>100 pg/mL), a ProGRP decline after Cycle 2 was associated with nonprogression (area under the curve: 84%; 95% confidence interval: 72.8-95.1; n = 141). ProGRP changes from baseline to end of Cycle 1 were predictive of response, as determined by computed tomography scan 3 weeks later (area under the curve: 87%; 95% confidence interval: 74.1-99.2; n = 137). This was enhanced by repeat measurements, with a 92% area under the curve (95% confidence interval: 85.3-97.8) among patients with ProGRP data after both Cycles 1 and 2 (n = 123); if a patient experienced a ≥25% decline in ProGRP after Cycle 1, and ProGRP remained stable or decreased after Cycle 2, the probability of finding progression on the interim computed tomography scan at the end of Cycle 2 was almost zero (sensitivity: 100%, specificity: 71%). Both ProGRP levels at baseline and at the end of first-line chemotherapy were prognostic; the latter provided a moderately improved hazard ratio of 2.43 (95% confidence interval: 1.33-4.46; n = 110) versus 1.87 (95% confidence interval: 1.04-3.37; n = 216). In summary, for patients with small-cell lung cancer and elevated baseline ProGRP levels, ProGRP may be a simple, reliable, and repeatable tool for monitoring response to chemotherapy and provide valuable prognostic information.


Assuntos
Neoplasias Pulmonares/sangue , Fragmentos de Peptídeos/sangue , Carcinoma de Pequenas Células do Pulmão/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Biomarcadores Tumorais/sangue , China , Europa (Continente) , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Recombinantes/sangue , Sensibilidade e Especificidade , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Tomografia Computadorizada por Raios X
7.
Rev. esp. med. nucl. imagen mol. (Ed. impr.) ; 39(1): 9-13, ene.-feb. 2020. ilus, tab, graf
Artigo em Espanhol | IBECS | ID: ibc-195940

RESUMO

OBJETIVO: El propósito del presente estudio es determinar el valor pronóstico de los parámetros metabólicos relacionados con los tumores primarios detectados en los exámenes por tomografía por emisión de positrones/tomografía computarizada (PET/TC) del pretratamiento flúor-18 2-fluoro-2-desoxi-D-glucosa (18F FDG) de pacientes a los que se les ha diagnosticado cáncer pulmonar de células pequeñas (SCLC, por sus siglas en inglés). MATERIALES Y MÉTODOS: En este estudio retrospectivo se inscribieron 63 pacientes con un diagnóstico histopatológicamente confirmado de SCLC a los que se les aplicó un escáner PET/TC con 18F FDG en la línea basal. Se registraron la etapa de la enfermedad, la edad en su diagnóstico, el sexo, el nivel de albúmina y el valor máximo de captación estándar (SUVmax), SUVmean, el volumen de tumor metabólico (MTV) y los valores de glucólisis total de la lesión) relacionados con el tumor primario en el escáner PET de línea basal y se evaluó la relación de estos factores con la supervivencia libre de progresión (PFS) y la supervivencia global (OS). RESULTADOS: El estudio incluyó un total de 63 pacientes (10 mujeres, 53 hombres, con una edad media de 64,8 y un rango de edad de 43-82 años), 22 de los cuales tenía enfermedad limitada (LD) y 41 tenía enfermedad extendida (ED). Los OS y PFS fueron significativamente mayores en pacientes con LD que en pacientes con ED (15+/-2,9 ante 10+/-0,9 meses, p = 0,002 para OS; 10+/- 0,7 ante 6+/-0,6 meses, p = 0,014 para PFS). Sin embargo, no se identificó una relación estadísticamente significativa entre el sexo, el nivel de albúmina, la edad y los niveles SUVmax, SUVmean, MTV y TLG relacionados con el tumor primario y PFS u OS. CONCLUSIÓN: El presente estudio descubrió que los parámetros PET del pretratamiento no tenían valor predictivo para el PFS y OS en pacientes con SCLC


OBJECTIVE: The aim in the present study is to determine the prognostic value of metabolic parameters related to the primary tumors detected in pretreatment Fluorine-18 2-fluoro-2-Deoxy-D-glucose (18F FDG) positron emission tomography/computerized tomography (PET/CT) scans of patients diagnosed with small-cell lung cancer (SCLC). MATERIAL AND METHODS: Enrolled in this retrospective study were 63 patients with a histopathologically confirmed diagnosis of SCLC who underwent an 18F FDG PET/CT scan at baseline. Disease stage, age at diagnosis, gender, albumin level and maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) values related to the primary tumor at the baseline PET scan were recorded, and the relationship of these factors with progression-free survival (PFS) and overall survival (OS) was evaluated. RESULTS: The study included a total of 63 patients (10 female, 53 male, mean age of 64.8 and age range of 43-82 years), 22 of which had limited disease (LD) and 41 had extensive disease (ED). The OS and PFS were significantly higher in patients with LD than in patients with ED (15+/-2.9 vs. 10+/-0.9 months, p = 0.002 for OS; 10+/- 0.7 vs 6+/-0.6 months, p = 0.014 for PFS). However, no statistically significant relationship was identified between gender, albumin level, age and SUVmax, SUVmean, MTV, TLG values related to the primary tumor and PFS or OS. CONCLUSION: The present study found that pretreatment PET parameters were of not predictive value for PFS and OS in patients with SCLC


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/mortalidade , Tomografia Computadorizada por Raios X , Compostos Radiofarmacêuticos , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/mortalidade , Fatores Etários , Fluordesoxiglucose F18/farmacocinética , Glicólise , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Tomografia por Emissão de Pósitrons , Prognóstico , Intervalo Livre de Progressão , Compostos Radiofarmacêuticos/farmacocinética , Estudos Retrospectivos , Fatores Sexuais , Carcinoma de Pequenas Células do Pulmão/metabolismo , Carcinoma de Pequenas Células do Pulmão/patologia
8.
Radiat Oncol ; 15(1): 14, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31937336

RESUMO

INTRODUCTION: Limited stage small cell lung cancer (LS-SCLC) has a poor prognosis. Additional prognostic markers are needed for risk-stratification and treatment intensification. This study compares quantitative CT-based volumetric tumor measurements versus International Association for the Study of Lung Cancer (IASLC) TNM staging to predict outcomes. MATERIALS & METHODS: A cohort of 105 patients diagnosed with LS-SCLC and treated with chemoradiation (CRT) from 2000 to 2013 were analyzed retrospectively. Patients were staged by the Union for International Cancer Control (UICC) TNM Classification, 8th edition. Tumor volumes and diameters were extracted from radiation planning CT imaging. Univariable and multivariable models were used to analyze relationships between CT features and overall survival (OS), locoregional recurrence (LRR), in-field LRR, any progression, and distant metastasis (DM). RESULTS: Median follow-up was 21.3 months. Two-year outcomes were as follows: 38% LRR, 31% in-field LRR, 52% DM, 62% any progression, and 47% OS (median survival 16.5 months). On univariable analysis, UICC T-stage and N-stage were not associated with any clinical outcome. UICC overall stage was only statistically associated with in-field LRR. One imaging feature (3D maximum tumor diameter) was found to be significantly associated with LRR (HR 1.10, p = 0.003), in-field LRR (HR 1.10, p = 0.007), DM (HR 1.10, p = 0.02), any progression (HR 1.10, p = 0.008), and OS (HR 1.10, p = 0.03). On multivariable analysis, this feature remained significantly associated with all outcomes. CONCLUSION: For LS-SCLC, quantitative CT-based volumetric tumor measurements were significantly associated with outcomes after CRT and may be better predictors of outcome than TNM stage.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Neoplasias Pulmonares/diagnóstico por imagem , Planejamento da Radioterapia Assistida por Computador , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/patologia , Resultado do Tratamento , Carga Tumoral/efeitos da radiação
9.
Intern Med ; 59(5): 701-704, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31708544

RESUMO

Invasion of the endobronchial mucosa by cancer cells is frequently seen in small cell lung cancer (SCLC), but an intraluminal polypoid growth pattern is extremely rare. We herein describe the case of a 69-year-old woman with limited-stage SCLC who had a pedunculated mass in the orifice of the right upper bronchus. Thin-section CT of the lung showed an endobronchial protruding mass accompanied by tubular and branching opacities (the so-called finger-in-glove sign) in the right upper lobe bronchus, which were enhanced by contrast media. She responded well to chemotherapy with concurrent radiation therapy. Although very rare, SCLC patients can have intraluminal polypoid growth, as was observed in this case.


Assuntos
Neoplasias Pulmonares/patologia , Carcinoma de Pequenas Células do Pulmão/patologia , Idoso , Brônquios/patologia , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Pólipos/patologia , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem
10.
Cancer Radiother ; 23(6-7): 701-707, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31501024

RESUMO

Lung cancer treatment is a heavy workload for radiation oncologist and that field showed many evolutions over the last two decades. The issue about target volume was raised when treatment delivery became more precise with the development of three-dimensional conformal radiotherapy. Initially based upon surgical series, numerous retrospective and prospective studies aimed to evaluate the risk of elective nodal failure of involved-field radiotherapy compared to standard large field elective nodal irradiation. In every setting, locally advanced non-small cell lung cancer, localized non-small cell lung cancer, localized small cell lung cancer, exclusive chemoradiation or postoperative radiotherapy, most of the studies showed no significant difference between involved-field radiotherapy or elective nodal irradiation with elective nodal failure rate under 5% at 2 years, provided staging had been done with modern imaging and diagnostic techniques (positron emission tomography scan, endoscopy, etc.). Moreover, if reducing irradiated volumes are safe regarding recurrences, involved-field radiotherapy allowed dose escalation while reducing acute and late oesophageal, cardiac and pulmonary toxicities. Consequently, major clinical trials involving radiotherapy initiated in the last two decades and international clinical guidelines recommended omission of elective nodal irradiation in favour of in-field radiotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Irradiação Linfática/métodos , Radioterapia Conformacional/métodos , Carcinoma de Pequenas Células do Pulmão/radioterapia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Tomografia por Emissão de Pósitrons , Radioterapia/métodos , Radioterapia de Intensidade Modulada/métodos , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/patologia , Toracoscopia
12.
Medicine (Baltimore) ; 98(35): e16593, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464894

RESUMO

RATIONALE: Limbic encephalitis is one of the most common paraneoplastic neurological disorders (PND). The role of brain Fluorine-18-fluorodeoxyglucose position emission tomography/computed tomography (CT) in paraneoplastic limbic encephalitis (PLE) and of the whole body 18F-FDG PET/CT in this setting, remains still not well defined. PATIENT CONCERNS: We report a case of a patient with chronic inflammatory rheumatism, psoriasis and Hashimoto thyroiditis and subsequent appearance of static and dynamic ataxia and episodic memory deficit who was diagnosed as PLE combined with small cell lung cancer (SCLC). DIAGNOSES: The diagnosis of SCLC was made with EBUS-TBNA of a mediastinal lymph node. INTERVENTIONS: Whole-body 18F-FDG PET/CT was performed for the initial staging of SCLC, in the planning of radiotherapy treatment, to evaluate therapeutic response and in the follow-up. A dedicated brain scan was included to the same PET session. Whole-body contrast enhanced computed tomography (CT) and contrast enhanced whole-brain MRI were also performed. OUTCOMES: She was administered neoadjuvant chemioterapy with Cisplatin and Etoposide with concomitant radiotherapy treatment. Whole body 18F-FDG PET/CT showed a complete metabolic response already after 3 cycles of chemioterapy. Brain functional study showed a metabolic pattern characterized by the migration of hypermetabolism in the bilateral hippocampal areas during the therapeutic treatment, which correlated with the persistence of clinical symptoms. LESSONS: In the era of personalized medicine and targeted therapy, this case highlights the importance of the 18F-FDG PET/CT study as an accurate tool to identify PLE and to guide the diagnostic work-up of the underlying tumor. Considering that most of these are 18F-FDG avid tumors and that the 18F-FDG PET/CT scan is often added to the diagnostic work-up when screening patients for malignancy, this functional imaging can play a decisive role.


Assuntos
Fluordesoxiglucose F18/administração & dosagem , Encefalite Límbica/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Encéfalo/diagnóstico por imagem , Cisplatino/uso terapêutico , Etoposídeo/uso terapêutico , Feminino , Humanos , Encefalite Límbica/tratamento farmacológico , Encefalite Límbica/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Terapia Neoadjuvante , Estadiamento de Neoplasias , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Resultado do Tratamento , Imagem Corporal Total
13.
BMJ Case Rep ; 12(7)2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31315840

RESUMO

Paraneoplastic syndromes (PS) are a rare presentation of cancer, most commonly associated with small cell lung cancer (SCLC), breast cancer and haematologic malignancies. The diagnosis of PS is challenging because it could affect multiple organ systems and it may present before the tumour is visible by imaging. We report a malignant tumour diagnosed in a male patient who referred long-term paraesthesia and proximal muscle strength loss. After ruling out common causes of polyneuropathy, the anti-SOX1 antibody gave light to the diagnosis. A pulmonary opacity in the upper right lobe was observed in the chest X-ray and a pulmonary tumour was later confirmed by CT scan. The biopsy of the cervical lymphadenopathy determined an SCLC, which caused a PS called Lambert-Eaton myasthenic syndrome (LEMS). Our case raises awareness of a rare PS presentation, which can be diagnosed by specific antibodies, allowing early diagnosis and treatment of lung cancer.


Assuntos
Síndrome Miastênica de Lambert-Eaton/sangue , Síndromes Paraneoplásicas/diagnóstico , Parestesia/etiologia , Fatores de Transcrição SOXB1/antagonistas & inibidores , Carcinoma de Pequenas Células do Pulmão/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Autoanticorpos/sangue , Diagnóstico Diferencial , Eletromiografia/métodos , Humanos , Síndrome Miastênica de Lambert-Eaton/complicações , Síndrome Miastênica de Lambert-Eaton/diagnóstico , Masculino , Síndromes Paraneoplásicas/fisiopatologia , Fatores de Transcrição SOXB1/sangue , Biópsia de Linfonodo Sentinela/métodos , Carcinoma de Pequenas Células do Pulmão/complicações , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
14.
Clin Nucl Med ; 44(9): 687-694, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31274560

RESUMO

PURPOSE: This pilot study aimed to prove the complementary value of a novel Gallium-labeled heterodimeric peptide, Ga-NOTA-3P-TATE-RGD, in detection and evaluation of tumors with somatostatin receptor subtype 2 or integrin αvß3 overexpression, including non-small cell lung cancer (NSCLC), small-cell lung cancer (SCLC), neuroendocrine tumor (NET), and neuroendocrine carcinoma (NEC). METHODS: With institute review board approval and written informed consent, 32 patients with pathologically diagnosed lung cancer (18 NSCLC, 14 SCLC) and 12 patients with neuroendocrine neoplasm (8 NET, 4 NEC) patients were recruited to undergo Ga-NOTA-3P-TATE-RGD PET/CT. For comparison, the NSCLC patients also underwent Ga-NOTA-TATE PET/CT, the SCLC patients underwent Ga-NOTA-RGD PET/CT, and the neuroendocrine neoplasm patients underwent F-FDG PET/CT within 3 days. The maximum standardized uptake value (SUV) of the primary tumor (T) and mean SUV of the blood pool (B) were measured, and the T/B ratios were calculated for comparison. RESULTS: In the primary tumors of NSCLC, the T/B ratios of Ga-NOTA-3P-TATE-RGD were significantly higher than those of Ga-NOTA-TATE (4.54 ± 3.00 versus 4.10 ± 2.83, P = 0.0058). In SCLC, the T/B ratios of Ga-NOTA-3P-TATE-RGD were significantly higher than those of Ga-NOTA-RGD (6.06 ± 6.09 versus 2.65 ± 1.19, P = 0.0344). In NET, the T/B ratios of Ga-NOTA-3P-TATE-RGD were 36.13 ± 33.84, significantly higher than those of F-FDG (2.91 ± 1.71, P = 0.0234). In NEC, there were no significant difference between the T/B ratios of Ga-NOTA-3P-TATE-RGD (4.80 ± 0.85) and those of F-FDG (3.56 ± 0.74, P = 0.1833). CONCLUSIONS: This proof-of-concept study preliminarily demonstrates the efficacy of the dual targeting Ga-NOTA-3P-TATE-RGD PET/CT in the evaluation of lung cancer and neuroendocrine neoplasm in a single scan.


Assuntos
Integrina alfaVbeta3/metabolismo , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/metabolismo , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Receptores de Somatostatina/metabolismo , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/metabolismo
15.
Acta Oncol ; 58(10): 1378-1385, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31271079

RESUMO

Introduction: Inter-observer variability (IOV) in target volume delineation is a well-documented source of geometric uncertainty in radiotherapy. Such variability has not yet been explored in the context of adaptive re-delineation based on imaging data acquired during treatment. We compared IOV in the pre- and mid-treatment setting using expert primary gross tumour volume (GTV) and clinical target volume (CTV) delineations in locoregionally advanced head-and-neck squamous cell carcinoma (HNSCC) and (non-)small cell lung cancer [(N)SCLC]. Material and methods: Five and six observers participated in the HNSCC and (N)SCLC arm, respectively, and provided delineations for five cases each. Imaging data consisted of CT studies partly complemented by FDG-PET and was provided in two separate phases for pre- and mid-treatment. Global delineation compatibility was assessed with a volume overlap metric (the Generalised Conformity Index), while local extremes of IOV were identified through the standard deviation of surface distances from observer delineations to a median consensus delineation. Details of delineation procedures, in particular, GTV to CTV expansion and adaptation strategies, were collected through a questionnaire. Results: Volume overlap analysis revealed a worsening of IOV in all but one case per disease site, which failed to reach significance in this small sample (p-value range .063-.125). Changes in agreement were propagated from GTV to CTV delineations, but correlation could not be formally demonstrated. Surface distance based analysis identified longitudinal target extent as a pervasive source of disagreement for HNSCC. High variability in (N)SCLC was often associated with tumours abutting consolidated lung tissue or potentially invading the mediastinum. Adaptation practices were variable between observers with fewer than half stating that they consistently adapted pre-treatment delineations during treatment. Conclusion: IOV in target volume delineation increases during treatment, where a disparity in institutional adaptation practices adds to the conventional causes of IOV. Consensus guidelines are urgently needed.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias Pulmonares/radioterapia , Planejamento da Radioterapia Assistida por Computador/estatística & dados numéricos , Carcinoma de Pequenas Células do Pulmão/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Fracionamento da Dose de Radiação , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Variações Dependentes do Observador , Tomografia por Emissão de Pósitrons , Planejamento da Radioterapia Assistida por Computador/métodos , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Carga Tumoral/efeitos da radiação
16.
J Biophotonics ; 12(9): e201900061, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31177622

RESUMO

This paper summarizes results from two large lung cancer studies comprising over 700 samples that demonstrate the ability of spectral histopathology (SHP) to distinguish cancerous tissue regions from normal tissue, to differentiate benign lesions from normal tissue and cancerous lesions, and to classify lung cancer types. Furthermore, malignancy-associated changes can be identified in cancer-adjacent normal tissue. The ability to differentiate a multitude of normal cells and tissue types allow SHP to identify tumor margins and immune cell infiltration. Finally, SHP easily distinguishes small cell lung cancer (SCLC) from non-SCLC (NSCLC) and provides a further differentiation of NSCLC into adenocarcinomas and squamous cell carcinomas with an accuracy comparable of classical histopathology combined with immunohistochemistry. Case studies are presented that demonstrates that SHP can resolve interobserver discrepancies in standard histopathology.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma de Células Escamosas/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Análise por Conglomerados , Análise de Fourier , Humanos , Imuno-Histoquímica , Macrófagos/citologia , Neoplasias/diagnóstico por imagem , Variações Dependentes do Observador , Filogenia , Análise de Componente Principal , Valores de Referência , Espectrofotometria Infravermelho , Análise Serial de Tecidos
17.
J Med Case Rep ; 13(1): 187, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31217026

RESUMO

BACKGROUND: Radiotherapy has been shown to cause malfunction of implantable cardioverter-defibrillators, and there are few studies of implantable cardioverter-defibrillators and radiotherapy. We report an unusual case of small cell lung cancer in a patient with an implantable cardioverter-defibrillator in whom direct irradiation to the electrode and lead could not be avoided. CASE PRESENTATION: We report a case of radiotherapy in a 72-year-old Korean man with a limited stage of small cell lung cancer who had undergone insertion of an implantable cardioverter-defibrillator because of ventricular fibrillation. The radiation dose was 60 Gy in 30 fractions to the thorax. The mean dose and maximum dose estimated at the body of the implantable cardioverter-defibrillator were 0.89 Gy and 2.23 Gy, respectively. The mean and maximum doses of the lead and electrode were 17.12 Gy and 55.72 Gy in the lead and 1.81 Gy and 7.10 Gy in the electrode, respectively, because part of the lead and electrode was inevitably in the irradiated fields. The function of the patient's implantable cardioverter-defibrillator was checked daily, and no change in implantable cardioverter-defibrillator function was observed for the duration of radiotherapy. The patient was tolerated the treatment well without severe complications. Computed tomography performed at 4 weeks after radiotherapy showed a good response with regression of the tumor. The patient was alive with complete remission of the tumor and without any implantable cardioverter-defibrillator dysfunction more than 36 months after the end of treatment. CONCLUSIONS: This case demonstrates that radiotherapy may be a safe and effective treatment modality through careful monitoring of implantable cardioverter-defibrillators in patients with lung cancer who have implantable cardioverter-defibrillators.


Assuntos
Desfibriladores Implantáveis , Neoplasias Pulmonares/radioterapia , Carcinoma de Pequenas Células do Pulmão/radioterapia , Idoso , Fracionamento da Dose de Radiação , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Doses de Radiação , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem
18.
Clin Cancer Res ; 25(16): 5107-5121, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31164374

RESUMO

PURPOSE: Small-cell lung cancer (SCLC) has been treated clinically as a homogeneous disease, but recent discoveries suggest that SCLC is heterogeneous. Whether metabolic differences exist among SCLC subtypes is largely unexplored. In this study, we aimed to determine whether metabolic vulnerabilities exist between SCLC subtypes that can be therapeutically exploited. EXPERIMENTAL DESIGN: We performed steady state metabolomics on tumors isolated from distinct genetically engineered mouse models (GEMM) representing the MYC- and MYCL-driven subtypes of SCLC. Using genetic and pharmacologic approaches, we validated our findings in chemo-naïve and -resistant human SCLC cell lines, multiple GEMMs, four human cell line xenografts, and four newly derived PDX models. RESULTS: We discover that SCLC subtypes driven by different MYC family members have distinct metabolic profiles. MYC-driven SCLC preferentially depends on arginine-regulated pathways including polyamine biosynthesis and mTOR pathway activation. Chemo-resistant SCLC cells exhibit increased MYC expression and similar metabolic liabilities as chemo-naïve MYC-driven cells. Arginine depletion with pegylated arginine deiminase (ADI-PEG 20) dramatically suppresses tumor growth and promotes survival of mice specifically with MYC-driven tumors, including in GEMMs, human cell line xenografts, and a patient-derived xenograft from a relapsed patient. Finally, ADI-PEG 20 is significantly more effective than the standard-of-care chemotherapy. CONCLUSIONS: These data identify metabolic heterogeneity within SCLC and suggest arginine deprivation as a subtype-specific therapeutic vulnerability for MYC-driven SCLC.


Assuntos
Arginina/metabolismo , Metabolismo Energético , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/metabolismo , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Redes e Vias Metabólicas , Camundongos , Camundongos Transgênicos , Modelos Biológicos , Transdução de Sinais , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/patologia , Serina-Treonina Quinases TOR/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Cancer Biol Ther ; 20(9): 1172-1175, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31161851

RESUMO

Patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer can benefit significantly from EGFR tyrosine-kinase inhibitors (TKIs) treatment, but almost every patient will inevitably develop resistance. The transformation to small cell lung cancer (SCLC) has been described as an EGFR-TKI resistance often associated with aggressive clinical course and poor prognosis. In this study, we report an unexpected favorable response to etoposide and cisplatin (EP) from an EGFR-mutant patient who developed SCLC transformation at disease progression after the administration of erlotinib with a progression-free survivalof 7.7 months. At disease progression (PD) after erlotinib, rebiopsy showed typical SCLC histology accompanied by positive expressions of CD56, TTF-1, CK7, and synaptophysin. Subsequently, he was switched to standard SCLC treatment regimen EP in combination with erlotinib due to the retention of EGFR 19 del and achieved PR four cycles after the treatment. His disease progressed again 7.7 months after the initiation of EP treatment, with an enlargement of both primary and metastatic lesions. Collectively, this case illustrated the transformation from adenocarcinoma to SCLC and the subsequent durable benefit from standard treatment for SCLC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais , Transformação Celular Neoplásica/genética , Cisplatino/administração & dosagem , Resistencia a Medicamentos Antineoplásicos , Etoposídeo/administração & dosagem , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/genética , Resultado do Tratamento
20.
J Thorac Oncol ; 14(10): 1743-1752, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31195178

RESUMO

INTRODUCTION: Inhibitors of poly-(ADP)-ribose polymerase (PARP) are promising therapeutics for SCLC. We tested whether PARP inhibitor (PARPi) target engagement as measured by a fluorine 18-radiolabeled PARPi ([18F]PARPi) has the potential to predict drug efficacy in vivo. METHODS: Tumor growth inhibition during daily talazoparib treatment was evaluated in mice engrafted with SCLC patient-derived xenografts to evaluate talazoparib efficacy at multiple doses. Mice were intravenously injected with [18F]PARPi radiotracer at multiple timepoints after single doses of oral talazoparib to quantitatively assess the extent to which talazoparib could reduce tumor radiotracer uptake and positron-emission tomographic (PET)/computer tomographic activity. Tumors were harvested and tumor poly-(ADP) ribose level was measured by enzyme-linked immunosorbent assay. RESULTS: A dose range of talazoparib with differential therapeutic efficacy was established, with significant delay in time to reach 1000 mm3 for tumors treated with 0.3 mg/kg (p = 0.02) but not 0.1 mg/kg talazoparib. On PET/computed tomography with [18F]PARPi, reduction in [18F]PARPi uptake after talazoparib dosing was consistent with talazoparib clearance, with reduction in PET activity attenuating over 24 hours. Talazoparib target engagement, measured by maximum tumor PET uptake, increased in a dose-dependent manner (3.9% versus 2.1% injected dose/g for 0.1 and 0.3 mg/kg at 3 hours post-talazoparib, p = 0.003) and correlated with PARP enzymatic activity among individual tumors as measured by total tumor poly-(ADP) ribose (p = 0.04, R = 0.62 at 1 hour post-talazoparib). CONCLUSIONS: PET imaging using [18F]PARPi has the potential to be a powerful tool in treatment monitoring by assessing PARPi target engagement in real-time.


Assuntos
Radioisótopos de Flúor/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Ftalazinas/farmacologia , Poli(ADP-Ribose) Polimerase-1/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Tomografia por Emissão de Pósitrons/métodos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Animais , Apoptose , Proliferação de Células , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Compostos Radiofarmacêuticos/metabolismo , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/metabolismo , Carcinoma de Pequenas Células do Pulmão/patologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
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