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1.
JCO Glob Oncol ; 8: e2200061, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36351211

RESUMO

PURPOSE: Stereotactic body radiation therapy (SBRT) is an effective option for patients with both early-stage and oligometastatic non-small-cell lung cancer (NSCLC). However, data from Latin America are limited. Therefore, the aim of this study was to investigate the real-world outcomes of applying SBRT for lung lesions in a Brazilian institution. METHODS: This study investigated a consecutive cohort of patients treated with SBRT for lung lesions (primary and metastasis). The study primary outcome was local control rates per lesion. Secondary outcomes included progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: Between 2015 and 2019, a total of 216 patients received SBRT and were included in the study. The median follow-up was 24.5 months (5-70), primary NSCLC corresponded to 70% (n = 151) and nonprimary lung lesions to 30% (n = 65), respectively. Stage I NSCLC represented 56% (85 of 151) of the NSCLC cohort. The average number of fractions and total dose prescribed was 5 (3-10)/59 Gy (50-62 Gy). For stage I NSCLC (all lesions treated with a biologically effective dose [10] > 100 Gy), 2-year local control, OS, and PFS were 93.4%, 81.6%, and 80.7%, respectively. For stage IV lesions, if biologically effective dose (10) > 100 Gy or < 100 Gy, 2-year local control was 95.8/86.4% (P = .03), 2-year-OS was 81.6/60.5% (P = .006), and 2-year PFS was 38.9/17.9% (P = .10). Late toxicity was observed in 16.2% (n = 35) of the total cases. CONCLUSION: Our results indicate that SBRT is effective (high local control and acceptable toxicity) for treating malignant lung lesions in a real-world scenario in Latin America.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Humanos , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Brasil/epidemiologia , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patologia , Pulmão/patologia , Intervalo Livre de Progressão
2.
BMC Pulm Med ; 22(1): 411, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36357868

RESUMO

OBJECTIVES: To compare overall survival (OS) and cancer-specific survival (CSS) outcomes of surgery with radiotherapy in octogenarians with stage Ia non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients aged ≥ 80 years with clinical stage Ia (T1N0M0) NSCLC between 2012 and 2017 were identified from the population-based Surveillance, Epidemiology, and End Results (SEER) database. Patients were assigned into surgery and radiotherapy groups. Multivariate Cox regression analysis was used to identify survival-associated factors. Treatment groups were adjusted by propensity score matching (PSM) analysis while OS and CSS outcomes were compared among groups by Kaplan-Meier analysis. RESULTS: A total of 1641 patients were identified, with 46.0% in the surgical group and 54.0% in the radiotherapy group. Compared to surgery, radiotherapy-treated patients were older, later diagnosed, had more often unmarried, more squamous cell carcinoma, more unknown grade and increased tumor sizes. Radiotherapy was associated with a significantly worse OS, compared to surgery (hazard ratio 2.426; 95% CI 2.003-2.939; P < .001). After PSM, OS (P < 0.001) and CSS (P < 0.001) were higher in the surgery group. The 1-, 3-, and 5-year OS rates of surgical and radiotherapy group were 90.0%, 76.9%, 59.9%, and 86.0%, 54.3%, 28.0%, respectively. The 1-, 3-, and 5-year CSS rates of surgical and radiotherapy group were 94.5%, 86.1%, 78.0% and 90.7%, 74.5%, 61.0%, respectively. There were no survival differences between the matched surgery without lymph node examination (LNE) and radiotherapy group, as well as between the matched surgery and radiotherapy who were recommended but refused surgery group. CONCLUSIONS: In octogenarians with stage Ia NSCLC, surgery with lymph node dissection offers better OS and CSS outcomes than radiotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Idoso de 80 Anos ou mais , Humanos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Pontuação de Propensão , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Octogenários , Programa de SEER , Estadiamento de Neoplasias
3.
Genes (Basel) ; 13(11)2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36360316

RESUMO

A new treatment modality targeting cuproptosis is gradually entering the public horizon. Cuproptosis is a new form of regulated cell death distinct from ferroptosis, apoptosis, autophagy, and necrosis. Previous studies have discovered that the copper level varies considerably in various cancers and that an increase in copper content is directly associated with the proliferation and metastasis of cancer cells. In non-small cell lung cancer (NSCLC) after radiation, the potential utility of cuproptosis-related long noncoding RNAs (lncRNAs) is still unclear. This research aimed to develop a prediction signature based on lncRNAs associated with cuproptosis to predict the prognosis of NSCLC patients following radiation. Methods: Expression data of primary tumors and adjacent solid tissues were downloaded from The Cancer Genome Atlas (TCGA) database, along with the corresponding clinical and mutational data. Univariate and multivariate COX analyses and LASSO regression analyses were performed to obtain a predictive signature of lncRNAs associated with cuproptosis. The data were randomly grouped into a training group used for model construction and a test group used for model validation. The model was validated by drawing a survival curve, risk curve, independent prognostic analysis, ROC curve PFS analysis, etc. Results: The lncRNA signature consisting of six cuproptosis-related lncRNAs (AC104088.1, PPP4R3B-DT, AC006042.3, LUCAT1, HHLA3-AS1, and LINC02029) was used to predict the prognosis of patients. Among them, there were three high-risk lncRNAs (LUCAT1, HHLA3-AS1, and LINC02029) with HR > 1 and three protective lncRNAs (AC104088.1, PPP4R3B-DT, and AC006042.3), with an HR < 1. Data analysis demonstrated that the cuproptosis-related lncRNA signatures could well predict the prognosis of NSCLC patients after radiation. Patients in the high-risk category receive a worse prognosis than those in the low-risk group. Cuproptosis-related risk prediction demonstrated better predictive qualities than age, gender, and pathological stage factors. Conclusion: The risk proposed model can independently predict the prognosis of NSCLC patients after radiotherapy, provide a foundation for the role of cuproptosis-related lncRNAs in NSCLC after radiotherapy, and provide a clinical strategy for radiotherapy combined with cuproptosis in NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Regulação Neoplásica da Expressão Gênica , Cobre/metabolismo , Estimativa de Kaplan-Meier , Perfilação da Expressão Gênica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia
4.
Rev Med Suisse ; 18(804): 2134-2142, 2022 Nov 16.
Artigo em Francês | MEDLINE | ID: mdl-36382973

RESUMO

Despite technical improvements concerning lung irradiation modalities, radiation-induced pneumonitis remains a usual complication, notably in the field of lung cancer treatment. This complication may remain asymptomatic but can also lead to respiratory distress. Thus, a low degree of suspicion and a comprehensive work-up is mandatory to evaluate the indication for specific treatment. In this article, we discuss the hypothesized pathophysiologic pathways, risk factors, clinical/radiological presentation and management.


Malgré les améliorations des techniques d'irradiation à l'étage thoracique, la pneumopathie radique (PpR) reste une complication fréquente, en particulier dans le cadre du traitement du cancer pulmonaire. Cette complication, qu'elle soit précoce ou tardive, peut demeurer silencieuse ou causer une détresse respiratoire potentiellement fatale. C'est pourquoi un faible degré de suspicion est nécessaire, de manière à débuter précocement un bilan d'investigation et décider de l'indication à un traitement spécifique. Dans cet article, nous discutons des hypothèses pathophysiologiques qui sous-tendent la PpR, des facteurs de risque de survenue, de la présentation clinique et radiologique, ainsi que de sa prise en charge.


Assuntos
Neoplasias Pulmonares , Pneumonia , Pneumonite por Radiação , Humanos , Pneumonite por Radiação/diagnóstico , Pneumonite por Radiação/epidemiologia , Pneumonite por Radiação/etiologia , Neoplasias Pulmonares/radioterapia , Pulmão , Fatores de Risco , Pneumonia/diagnóstico , Pneumonia/epidemiologia , Pneumonia/etiologia
7.
Radiat Oncol ; 17(1): 188, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36397060

RESUMO

BACKGROUND: This study was designed to establish radiation pneumonitis (RP) prediction models using dosiomics and/or deep learning-based radiomics (DLR) features based on 3D dose distribution. METHODS: A total of 140 patients with non-small cell lung cancer who received stereotactic body radiation therapy (SBRT) were retrospectively included in this study. These patients were randomly divided into the training (n = 112) and test (n = 28) sets. Besides, 107 dosiomics features were extracted by Pyradiomics, and 1316 DLR features were extracted by ResNet50. Feature visualization was performed based on Spearman's correlation coefficients, and feature selection was performed based on the least absolute shrinkage and selection operator. Three different models were constructed based on random forest, including (1) a dosiomics model (a model constructed based on dosiomics features), (2) a DLR model (a model constructed based on DLR features), and (3) a hybrid model (a model constructed based on dosiomics and DLR features). Subsequently, the performance of these three models was compared with receiver operating characteristic curves. Finally, these dosiomics and DLR features were analyzed with Spearman's correlation coefficients. RESULTS: In the training set, the area under the curve (AUC) of the dosiomics, DLR, and hybrid models was 0.9986, 0.9992, and 0.9993, respectively; the accuracy of these three models was 0.9643, 0.9464, and 0.9642, respectively. In the test set, the AUC of these three models was 0.8462, 0.8750, and 0.9000, respectively; the accuracy of these three models was 0.8214, 0.7857, and 0.8571, respectively. The hybrid model based on dosiomics and DLR features outperformed other two models. Correlation analysis between dosiomics features and DLR features showed weak correlations. The dosiomics features that correlated DLR features with the Spearman's rho |ρ| ≥ 0.8 were all first-order features. CONCLUSION: The hybrid features based on dosiomics and DLR features from 3D dose distribution could improve the performance of RP prediction after SBRT.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Aprendizado Profundo , Neoplasias Pulmonares , Pneumonite por Radiação , Radiocirurgia , Humanos , Pneumonite por Radiação/etiologia , Radiocirurgia/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Estudos Retrospectivos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia
8.
J Transl Med ; 20(1): 524, 2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36371220

RESUMO

OBJECTIVE: This paper intends to propose a method of using TransResSEUnet2.5D network for accurate automatic segmentation of the Gross Target Volume (GTV) in Radiotherapy for lung cancer. METHODS: A total of 11,370 computed tomograms (CT), deriving from 137 cases, of lung cancer patients under radiotherapy developed by radiotherapists were used as the training set; 1642 CT images in 20 cases were used as the validation set, and 1685 CT images in 20 cases were used as the test set. The proposed network was tuned and trained to obtain the best segmentation model and its performance was measured by the Dice Similarity Coefficient (DSC) and with 95% Hausdorff distance (HD95). Lastly, as to demonstrate the accuracy of the automatic segmentation of the network proposed in this study, all possible mirrors of the input images were put into Unet2D, Unet2.5D, Unet3D, ResSEUnet3D, ResSEUnet2.5D, and TransResUnet2.5D, and their respective segmentation performances were compared and assessed. RESULTS: The segmentation results of the test set showed that TransResSEUnet2.5D performed the best in the DSC (84.08 ± 0.04) %, HD95 (8.11 ± 3.43) mm and time (6.50 ± 1.31) s metrics compared to the other three networks. CONCLUSIONS: The TransResSEUnet 2.5D proposed in this study can automatically segment the GTV of radiotherapy for lung cancer patients with more accuracy.


Assuntos
Neoplasias Pulmonares , Tomografia Computadorizada por Raios X , Humanos , Tomografia Computadorizada por Raios X/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Processamento de Imagem Assistida por Computador/métodos
9.
Int J Mol Sci ; 23(21)2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36362359

RESUMO

Ionizing radiation (IR) has been shown to play a crucial role in the treatment of glioblastoma (GBM; grade IV) and non-small-cell lung cancer (NSCLC). Nevertheless, recent studies have indicated that radiotherapy can offer only palliation owing to the radioresistance of GBM and NSCLC. Therefore, delineating the major radioresistance mechanisms may provide novel therapeutic approaches to sensitize these diseases to IR and improve patient outcomes. This review provides insights into the molecular and cellular mechanisms underlying GBM and NSCLC radioresistance, where it sheds light on the role played by cancer stem cells (CSCs), as well as discusses comprehensively how the cellular dormancy/non-proliferating state and polyploidy impact on their survival and relapse post-IR exposure.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Glioblastoma , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Glioblastoma/genética , Glioblastoma/radioterapia , Tolerância a Radiação/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , Linhagem Celular Tumoral , Recidiva Local de Neoplasia
10.
J Cancer Res Ther ; 18(6): 1706-1715, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36412433

RESUMO

Aim: The aim of this study was to evaluate the performance of various radiobiological models in predicting the occurrence of acute esophagitis (AE) during radiation therapy (RT) of head, neck, and thoracic tumors with concurrent and sequential chemotherapy. According to recent studies, the probability of AE following RT by normal tissue complication probability models is predictable. Materials and Methods: A total of 100 patients with nasopharynx, larynx, Hodgkin's lymphoma, spinal metastases, and oral cavity and lung tumors were included in the study. Half of these patients were treated by concurrent chemo-radiotherapy (Con. CRT) and the other half were treated by radiotherapy alone or sequential chemo-radiotherapy (RT + seq. CRT). Radiobiological models of several types were used as follows,: Lyman-generalized equivalent uniform dose (gEUD), Lyman-MED, log-logistic, logit, and logistic. Parameters were estimated using maximum likelihood estimation, and models were compared using Akaike information criteria. Results: Based on follow-up data, the behavior of dose-response curves differed markedly between the Con. CRT and RT + seq. CRT groups. The best fit with clinical results was offered by the Lyman-MED model for the Con. CRT group and the Lyman-gEUD model for the RT + seq. CRT group. Depending on the model used, the parameter of D50 was considerably lower (up to three times) in the Con. CRT group compared to the RT + seq. CRT group. Conclusions: The incidence of AE significantly differed between the two treatment groups in all the models. New parameter estimates could be used for predicting the probability of acute esophagitis after chemo-RT.


Assuntos
Esofagite , Laringe , Neoplasias Pulmonares , Humanos , Esofagite/etiologia , Esofagite/patologia , Pescoço/patologia , Neoplasias Pulmonares/radioterapia , Laringe/patologia , Tórax/patologia
11.
Medicine (Baltimore) ; 101(46): e31665, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36401404

RESUMO

In advanced non-small cell lung cancer (NSCLC), the brain and bones are common metastatic sites, and the disease seriously affects the survival time and quality of life. For metastatic lesions with symptoms, local treatment often precedes systemic treatment. However, in clinical trials, patients with symptomatic brain or bone metastases are often excluded. Therefore, limited data are available on the efficacy of immune checkpoint inhibitors (ICIs) in those patients. We aimed to evaluate the effectiveness and safety of local radiotherapy followed by ICIs in driver gene-negative NSCLC patients with symptomatic local metastasis in the brain and bone. This is a 29-month 2 centered retrospective cohort study performed in China between March 2019 and August 2021. A total of 22 patients with advanced NSCLC were included. All patients received radiotherapy in the brain or bone before the administration of ICIs. For all patients, the overall response rate was 59.09%, the median progression-free survival (PFS) was 7.5 months, the PFS rate at 6 months was 72.73%, and the PFS rate at 1 year was 13.64%. Waterfall plots showed that tumor size was mostly reduced compared with baseline. The spider map showed that the tumor continued to shrink. In terms of symptom improvement, 100% pain control and 83.33% improvement were observed in epilepsy and neurological function. Sequential ICIs with local radiotherapy is effective for the treatment of patients with symptomatic brain and bone metastases of driver gene-negative NSCLC, which will benefit patients and improve their symptoms.


Assuntos
Neoplasias Ósseas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Estudos Retrospectivos , Qualidade de Vida , Neoplasias Ósseas/radioterapia , Encéfalo/patologia
12.
Front Endocrinol (Lausanne) ; 13: 959089, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36407316

RESUMO

Purpose: This study investigated the relationship between BRAFV600E mutation of the primary tumor and radioiodine avidity in lung metastases (LMs) and then further evaluated the impact of BRAFV600E mutation and radioiodine avidity status on the prognosis of papillary thyroid cancer (PTC) with LMs. Methods: Ninety-four PTC patients with LMs after total thyroidectomy and cervical lymph node dissection between January 2012 and September 2021 were retrospectively included. All patients received BRAFV600E mutation examination of primary tumors and radioactive iodine (RAI) therapy. The therapeutic response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) assessments (version 1.1). For patients with target lesions, the response was divided into complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD); for patients without target lesions, the response was divided into CR, non-CR/non-PD, and PD. In therapeutic response, PR and SD were classified as non-CR/non-PD for analysis. The chi-square test and logistic regression were used to analyze the impact factor on PD and mortality. Progression-free survival (PFS) and overall survival (OS) curves were constructed by the Kaplan-Meier method. Results: It was found that 21.2% (7/33) of patients with positive BRAFV600E mutation and 62.3% (38/61) of patients with negative BRAFV600E mutation had radioiodine-avid LMs (χ2 = 14.484, p = 0.000). Patients with positive BRAFV600E mutation are more likely to lose radioiodine avidity; the odds ratios (ORs) were 5.323 (95% CI: 1.953-14.514, p = 0.001). Finally, 25 patients had PD, and six patients died; loss of radioiodine avidity was the independent predictor for PD, and the ORs were 10.207 (95% CI: 2.629-39.643, p = 0.001); BRAFV600E mutation status was not correlated with PD (p = 0.602), whether in the radioiodine avidity group (p = 1.000) or the non-radioiodine avidity group (p = 0.867). Similarly, BRAFV600E mutation status was not correlated with mortality; only loss of radioiodine avidity was the unfavorable factor associated with mortality in univariate analyses (p = 0.030). Conclusion: Patients with LMs of PTC were more likely to lose radioiodine avidity when their primary tumor had positive BRAFV600E mutation; however, only radioiodine avidity and not BRAFV600E mutation status affected the clinical outcome of patients with lung metastatic PTC.


Assuntos
Neoplasias Pulmonares , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/radioterapia , Câncer Papilífero da Tireoide/diagnóstico , Proteínas Proto-Oncogênicas B-raf/genética , Radioisótopos do Iodo/uso terapêutico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Estudos Retrospectivos , Mutação , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/tratamento farmacológico
14.
Signal Transduct Target Ther ; 7(1): 354, 2022 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-36253371

RESUMO

Protein neddylation is catalyzed by a neddylation activating enzyme (NAE, E1), an E2 conjugating enzyme, and an E3 ligase. In various types of human cancers, the neddylation pathway is abnormally activated. Our previous study validated that the neddylation E2 UBE2F is a promising therapeutic target in lung cancer. Although the NAE inhibitor MLN4924/pevonedistat is currently under clinical investigation as an anti-cancer agent, there are no small molecules available that selectively target UBE2F. Here, we report, for the first time, the discovery, via structure-based virtual screen and chemical optimization, of such a small molecule, designated as HA-9104. HA-9104 binds to UBE2F, reduces its protein levels, and consequently inhibits cullin-5 neddylation. Blockage of cullin-5 neddylation inactivates cullin-RING ligase-5 (CRL5) activity, leading to accumulation of the CRL5 substrate, NOXA, to induce apoptosis. Moreover, HA-9104 appears to form the DNA adduct via its 7-azaindole group to induce DNA damage and G2/M arrest. Biologically, HA-9104 effectively suppresses the growth and survival of lung cancer cells and confers radiosensitization in both in vitro cell culture and in vivo xenograft tumor models. In summary, we discovered a small molecule, designated HA-9104, that targets the UBE2F-CRL5 axis with anti-cancer activity alone or in combination with radiation.


Assuntos
Apoptose , Neoplasias Pulmonares , Apoptose/genética , Linhagem Celular Tumoral , Proteínas Culina/genética , Proteínas Culina/metabolismo , Ciclopentanos , Adutos de DNA/uso terapêutico , Pontos de Checagem da Fase G2 do Ciclo Celular , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , Pirimidinas , Enzimas de Conjugação de Ubiquitina/genética , Enzimas de Conjugação de Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/genética
15.
Anticancer Drugs ; 33(10): e842-e849, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36206101

RESUMO

OBJECTIVE: Immunotherapy plus etoposide and platinum (EP)-based chemotherapy is the standard of care for patients with extensive stage-small cell lung carcinoma (ES-SCLC). In the era of immunotherapy, the role of thoracic radiotherapy for ES-SCLC remains unclear. METHODS: We retrospectively included ES-SCLC patients treated with first-line EP-based chemotherapy plus atezolizumab or durvalumab at Taichung Veterans General Hospital to evaluate the prognostic role and safety of thoracic radiotherapy. RESULTS: A total of 22 patients were included. The median age was 64 years and most of them were male and smokers. Sixteen patients (72.7%) received durvalumab, while the other 6 patients (27.3%) underwent atezolizumab treatment. Among these patients, 11 (50.0%) had a history of thoracic radiotherapy. There was no significant difference in baseline characteristics between patients with and without thoracic radiotherapy. In the overall population, the objective response rate to immunotherapy plus chemotherapy was 73.7%. The progression-free survival and overall survival were 6.0 months (95% CI: 4.0-7.9) and 13.8 months (95% CI: 8.0-19.6), respectively. The overall survival was significantly longer in patients with thoracic radiotherapy (not-reached [NR] [95% CI NR-NR] vs. 9.6 months [95% CI 2.5-16.6]), respectively ( P value by log-rank test <0.001). Both multivariate analysis and subgroup analysis specifically comparing patients with consolidative thoracic radiotherapy and patients with clinical benefits to systemic therapy who did not undergo thoracic radiotherapy indicated that thoracic radiotherapy improved survival. CONCLUSION: The real-world efficacy of EP-based chemotherapy plus atezolizumab or durvalumab was comparable with that of clinical trials. Thoracic radiotherapy may improve the outcome of ES-SCLC.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Etoposídeo , Feminino , Humanos , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Platina , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/radioterapia
16.
Biomed Phys Eng Express ; 8(6)2022 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-36206726

RESUMO

Objective.Feasibility of three-dimensional (3D) tracking of volumetric modulated arc therapy (VMAT) based on VMAT-computed tomography (VMAT-CT) has been shown previously by our group. However, 3D VMAT-CT is not suitable for treatments that involve significant target movement due to patient breathing. The goal of this study was to reconstruct four-dimensional (4D) VMAT-CT and evaluate the feasibility of tracking based on 4D VMAT-CT.Approach.Synchronized portal images of phantoms and linac log were both sorted into four phases, and VMAT-CT+ was generated in each phase by fusing reconstructed VMAT-CT and planning CT using rigid or deformable registration. Dose was calculated in each phase and was registered to the mean position planning CT for 4D dose reconstruction. Trackings based on 4D VMAT-CT+ and 4D cone beam CT (CBCT) were compared. Potential uncertainties were also evaluated.Main results.Tracking based on 4D VMAT-CT+ was accurate, could detect phantom deformation and/or change of breathing pattern, and was superior to that based on 4D CBCT. The impact of uncertainties on tracking was minimal.Significance.Our study shows it is feasible to accurately track position and dose based on 4D VMAT-CT for patients whose VMAT treatments are subject to respiratory motion. It will significantly increase the confidence of VMAT and is a clinically viable solution to daily patient positioning,in vivodosimetry and treatment monitoring.


Assuntos
Neoplasias Pulmonares , Radioterapia de Intensidade Modulada , Humanos , Radioterapia de Intensidade Modulada/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Estudos de Viabilidade , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Tomografia Computadorizada Quadridimensional/métodos
17.
Cancer Biol Ther ; 23(1): 1-8, 2022 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-36201632

RESUMO

Stereotactic body radiotherapy (SBRT) demonstrates excellent local control in early stage lung cancer, however a quarter of patients develop recurrence or distant metastasis. Transforming growth factor-beta (TGF-ß) supports metastasis and treatment resistance, and angiotensin receptor blockade (ARB) indirectly suppresses TGF-ß signaling. This study investigates whether patients taking ARBs while undergoing SBRT for early stage lung cancer exhibited improved overall survival (OS) or recurrence free survival (RFS) compared to patients not taking ARBs. This was a single institution retrospective analysis of 272 patients treated with SBRT for early stage lung cancer between 2009 and 2018. Patient health data was abstracted from the electronic medical record. OS and RFS were assessed using Kaplan-Meier method. Log-rank test was used to compare unadjusted survival between groups. Univariable and multivariable Cox proportional hazard regression models were used to estimate hazard ratios (HRs). Of 247 patients analyzed, 24 (10%) patients took ARBs for the duration of radiotherapy. There was no difference in mean age, median tumor diameter, or median biologic effective dose between patients taking ARBs or not. Patients taking ARBs exhibited increased OS (ARB = 96.7 mo.; no ARB = 43.3 mo.; HR = 0.25 [95% CI: 0.10 to 0.62, P = .003]) and increased RFS (median RFS, ARB = 64.3 mo.; No ARB = 35.1 mo.; HR = 0.26 [95% CI: 0.10 to 0.63, P = .003]). These effects were not seen in patients taking angiotensin converting enzyme inhibitors (ACEIs) or statins. ARB use while undergoing SBRT for early stage lung cancer may increase OS and RFS, but ACEI use does not show the same effect.


Assuntos
Produtos Biológicos , Carcinoma Pulmonar de Células não Pequenas , Inibidores de Hidroximetilglutaril-CoA Redutases , Neoplasias Pulmonares , Radiocirurgia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Produtos Biológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Radiocirurgia/métodos , Receptores de Angiotensina/uso terapêutico , Estudos Retrospectivos , Fator de Crescimento Transformador beta , Fatores de Crescimento Transformadores/uso terapêutico , Resultado do Tratamento
18.
Cancer Treat Rev ; 110: 102464, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36194908

RESUMO

BACKGROUND: Hypofractionated proton beam radiotherapy (PBT) is gaining attention in early-stage non-small cell lung cancer (ES-NSCLC). However, there is a large unmet need to define indications, prescription doses and potential adverse events of protons in this clinical scenario. Hence, the present work aims to provide a critical literature revision, and to investigate associations between fractionation schedules/ biological effective doses (BEDs), oncological outcomes and toxicities. MATERIALS AND METHODS: This systematic review and meta-analysis complied with the PRISMA recommendations. Inclusion criteria were: 1) curative-intent hypofractionated PBT for ES-NSCLC (≥3 Gy(RBE)/fraction), 2) report of the clinical outcomes of interest, 3) availability of full-text written in English. The bibliographic search was performed on the NCBI Pubmed, Embase and Scopus in September 2021; no other limitations were applied. The BED was calculated for each included study (α/ß = 10 Gy); the median BED for all studies was used as a threshold for stratifying selected evidence into "high" and "low"-dose subgroups. Heterogeneity was tested using chi-square statistics; inconsistency was measured with the I2 index. Pooled estimate was obtained by fitting both the fixed-effect and the DerSimonian and Laird random-effect model. RESULTS: Eight studies and 401 patients were available for the meta-analysis; median follow-up was 32.8 months. The median delivered BED was 105.6 Gy(RBE). A BED ≥ 105.6 Gy(RBE) consistently provided superior OS, CSS, DFS and LC rates (i.e.: 4-year OS: 0.56 [0.34-0.76] for BED < 105.6 Gy(RBE) and 0.78 [0.64-0.88] for BED ≥ 105.6 Gy(RBE)). The meta-analysis of proportions showed a comparable probability of developing acute grade ≥ 2 toxicity between the two groups, while the probability of any late grade ≥ 2 event was almost three-times greater for BED ≥ 105.6 Gy(RBE), with rib fractures being more common in the high dose group. CONCLUSION: Hypofractionated PBT is a safe and effective treatment option for ES-NSCLC; the delivery of BED ≥ 105.6 Gy(RBE) with advanced techniques for uncertainty management has been associated with improved oncological outcomes across all considered time points.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Terapia com Prótons , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Fracionamento da Dose de Radiação , Humanos , Neoplasias Pulmonares/radioterapia , Terapia com Prótons/efeitos adversos , Terapia com Prótons/métodos , Prótons
19.
Anticancer Res ; 42(10): 4805-4812, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36191986

RESUMO

BACKGROUND/AIM: Many patients with advanced lung cancer develop brain metastasis (BM); however, few reports confirming the efficacy of immune checkpoint inhibitors (ICIs) plus chemotherapy in non-small cell lung cancer (NSCLC) patients with symptomatic BM have been published. Therefore, we retrospectively evaluated the effects of chemoimmunotherapy in NSCLC patients who did or did not receive prior brain radiotherapy. PATIENTS AND METHODS: A total of 103 patients with advanced NSCLC who received ICIs plus chemotherapy at our hospital from January 2019 to July 2021 were retrospectively enrolled. RESULTS: Patients with BM tended to have shorter progression-free survival (PFS) and overall survival (OS) compared with patients without BM. The maximum size of BM and the proportion of patients with symptomatic BM were greater among patients who received brain radiotherapy before chemoimmunotherapy. However, patients who received prior brain radiotherapy had better PFS and OS compared with patients who did not receive prior brain radiotherapy. CONCLUSION: Patients who received prior brain radiotherapy experienced a superior therapeutic benefit of ICIs plus chemotherapy, including those with larger and more symptomatic BM.


Assuntos
Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Encéfalo/patologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Receptores ErbB/uso terapêutico , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos
20.
Anticancer Res ; 42(10): 4795-4804, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36191990

RESUMO

BACKGROUND/AIM: Recent studies described the safety and clinical utility of combined anti-programmed cell death protein-1 (anti-PD1) checkpoint inhibition with radiotherapy. However, long-term follow-up data are lacking. Abscopal effects have been hypothesized, though clinical proof is still scarce. PATIENTS AND METHODS: We analyzed the efficacy and toxicity of combined (stereotactic) radiotherapy and anti-PD1 in consecutive oligoprogressive melanoma and non-small cell lung cancer (NSCLC) patients who were irradiated for 1 to 3 progressive metastases during anti-PD-1 in our institute between January 2017 and January 2019 and verified one-dimensional RECIST measurements by volumetric assessments. RESULTS: Out of 361 patients, 11 melanoma and 5 NSCLC patients were included in this series. Radiotherapy was applied after a median of 11 months (range=1-30 months) from the start of anti-PD1 treatment. No increased risk of adverse events for the combined treatments was observed. With a median follow-up of 4.9 years since the start of anti-PD1, 69% of patients were alive. Six of 16 patients had stable disease after a median follow-up of 4.1 years after radiotherapy. Abscopal effects were suspected in three out of 16 patients. However, if volumetric assessment was used, two of these patients already had tumor shrinkage prior to radiotherapy, not detected by one-dimensional measurements. CONCLUSION: Stereotactic radiotherapy for oligoprogressive disease during PD1-inhibition can induce long-term disease control. Although abscopal effects were suspected in three patients, they were not confirmed with volumetric assessment in two patients. The discrepancy found between one-dimensional and volumetric response assessment argues for including volumetric assessment in further studies.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Melanoma , Radiocirurgia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Humanos , Imunoterapia/métodos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Melanoma/tratamento farmacológico , Melanoma/radioterapia , Radiocirurgia/métodos
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