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1.
Bull Cancer ; 107(5): 565-573, 2020 May.
Artigo em Francês | MEDLINE | ID: mdl-32245602

RESUMO

Modern high-precision radiotherapy techniques have recently incorporated the notion of anatomical variations of the patient during treatment and have tried to adapt the treatment planning to them. Adaptive radiotherapy for nasopharyngeal tumors is starting to prove its benefit nowadays. His interest is constantly being evaluated. The variations encountered during the treatment are both geometric and dosimetric. They are represented by a reduction in the macroscopic tumors volume, a change in its position and a consequent dosimetric impact. The changes also concern organs at risk with a reduction of glandular structure volumes, and a different position which increases their doses. Delivered doses to noble structures (brainstem and spinal cord) may also increase. However, difficulties are encountered in its realization. There is a problem to perfectly reproduce the patient position during the second acquisition, which impacts the fusion quality between the two CT scans. This generates an imprecision in the definition of the same treatment isocentre on the second scanner. Also, there is a difficulty in accumulated doses calculation. The indication of adaptive radiotherapy remains a subject of controversy. It should be proposed for a subgroup of patients who could benefit from this new strategy. We present here an update on the state of the art of adaptive radiotherapy for nasopharyngeal cancer.


Assuntos
Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Tronco Encefálico/efeitos da radiação , Humanos , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/patologia , Pescoço/anatomia & histologia , Órgãos em Risco/efeitos da radiação , Posicionamento do Paciente , Radioterapia/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Medula Espinal/efeitos da radiação , Carga Tumoral/efeitos da radiação , Perda de Peso
2.
Lasers Med Sci ; 35(1): 87-93, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31076924

RESUMO

Melanotic melanoma has high content of melanin and laser can destroy melanin-containing cells through thermal effect. In this study, the therapeutic effect of 808 nm laser therapy was investigated on B16-F10 melanoma tumor growth and tumor-bearing mice survival time. In addition, as laser can destroy melanin as the main cause of melanoma radioresistance, the effect of laser administration to enhance radiation therapy efficacy at B16-F10 cancer cells was evaluated in vitro and in vivo. Laser therapy (1 W/cm2 × 4 min) could cause significant (P < 0.05) inhibition of melanoma tumors' growth (~ 61%) and about three times increase of the tumor-bearing mice survival time in comparison with no-treatment group. In addition, the mice which were treated with 1 W/cm2 × 4 min laser administration plus 6 Gy megavoltage radiation therapy exhibited ~ 68% lesser tumors' volume and 27 days increase of survival time in comparison with 6 Gy irradiated tumor-bearing mice. Also, significantly higher (P < 0.05) tumor necrosis percentage was observed at the histopathological slides of 1 W/cm2 × 4 min laser + RT treated mice tumors (57 ± 12%) in comparison with radiation therapy group (31 ± 10%). Therefore, not only laser therapy can inhibit melanoma tumors' growth per se but also its combination with radiation therapy can cause a significant enhancement of radiation therapy efficacy. The laser administration can be used as a radiosensitizing method for melanotic melanoma radiation therapy.


Assuntos
Eletricidade , Terapia a Laser , Melanoma Experimental/radioterapia , Animais , Linhagem Celular Tumoral , Feminino , Melanoma Experimental/patologia , Camundongos Endogâmicos C57BL , Necrose , Radiossensibilizantes/farmacologia , Análise de Sobrevida , Carga Tumoral/efeitos da radiação
3.
BMC Cancer ; 19(1): 1075, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703572

RESUMO

BACKGROUND: Radiotherapy failure is a significant clinical challenge due to the development of resistance in the course of treatment. Therefore, it is necessary to further study the radiation resistance mechanism of HCC. In our early study, we have showed that the expression of Aurora-A mRNA was upregulated in HCC tissue samples or cells, and Aurora-A promoted the malignant phenotype of HCC cells. However, the effect of Aurora-A on the development of HCC radioresistance is not well known. METHODS: In this study, colony formation assay, MTT assays, flow cytometry assays, RT-PCR assays, Western blot, and tumor xenografts experiments were used to identify Aurora-A promotes the radioresistance of HCC cells by decreasing IR-induced apoptosis in vitro and in vivo. Dual-luciferase reporter assay, MTT assays, flow cytometry assays, and Western blot assay were performed to show the interactions of Aurora-A and NF-κB. RESULTS: We established radioresistance HCC cell lines (HepG2-R) and found that Aurora-A was significantly upregulated in those radioresistant HCC cells in comparison with their parental HCC cells. Knockdown of Aurora-A increased radiosensitivity of radioresistant HCC cells both in vivo and in vitro by enhancing irradiation-induced apoptosis, while upregulation of Aurora-A decreased radiosensitivity by reducing irradiation-induced apoptosis of parental cells. In addition, we have showed that Aurora-A could promote the expression of nuclear IkappaB-alpha (IκBα) protein while enhancing the activity of NF-kappaB (κB), thereby promoted expression of NF-κB pathway downstream effectors, including proteins (Mcl-1, Bcl-2, PARP, and caspase-3), all of which are associated with apoptosis. CONCLUSIONS: Aurora-A reduces radiotherapy-induced apoptosis by activating NF-κB signaling, thereby contributing to HCC radioresistance. Our results provided the first evidence that Aurora-A was essential for radioresistance in HCC and targeting this molecular would be a potential strategy for radiosensitization in HCC.


Assuntos
Aurora Quinase A/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/radioterapia , NF-kappa B/metabolismo , Tolerância a Radiação/genética , Animais , Apoptose/genética , Apoptose/efeitos da radiação , Aurora Quinase A/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Células Hep G2 , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Inibidor de NF-kappaB alfa/metabolismo , Transdução de Sinais/genética , Transfecção , Carga Tumoral/genética , Carga Tumoral/efeitos da radiação
4.
Colloids Surf B Biointerfaces ; 184: 110496, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31525600

RESUMO

A greener approach for the design of surface plasmon resonant gold nanoparticles has been obtained with a hydrosoluble fraction of an endemic asteraceae medicinal plant. This medicinal plant is originated from Indian Ocean and demonstrates its bioreducing activity in the design of stable green nanomedicine in aqueous media. This article describes the preclinical assessment of the efficacy of these novel nanocandidates on murine model by intratumoral and intravenous injections. It definitely demonstrates two key points in the treatment of cancer: 1) optimization of the tumor microenvironment targeting by specific ligands for a limited damage on healthy tissue, 2) the need to screen the specific irradiation dose (time, power) taking into account the type of tumor.


Assuntos
Ouro/química , Química Verde/métodos , Nanopartículas Metálicas/química , Ressonância de Plasmônio de Superfície/métodos , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Asteraceae/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Ouro/administração & dosagem , Ouro/farmacocinética , Humanos , Injeções Intralesionais , Injeções Intravenosas , Luz , Nanopartículas Metálicas/administração & dosagem , Camundongos , Nanomedicina/métodos , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Neoplasias Experimentais/terapia , Fototerapia/métodos , Estudo de Prova de Conceito , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/efeitos da radiação
5.
J Radiat Res ; 60(6): 747-758, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31504707

RESUMO

This study examines the ability of arabinoxylan rice bran (MGN-3/Biobran) to enhance the anti-cancer effects of fractionated X-ray irradiation of Ehrlich solid tumor-bearing mice. Swiss albino mice bearing tumors were exposed to the following: (i) Biobran treatment (40 mg/kg/day, intraperitoneal injections) beginning on day 11 post-tumor cell inoculation until day 30; (ii) ionizing radiation (Rad) 2 Gy at three consecutive doses on days 12, 14 and 16; or (iii) Biobran + Rad. Final tumor weight was suppressed by 46% for Biobran, 31% for Rad and 57% for the combined treatment (Biobran + Rad) relative to control untreated mice. Biobran and Rad also arrested the hypodiploid cells in the sub-G1-phase, signifying apoptosis by +102% and +85%, respectively, while the combined treatment induced apoptosis by +123%, with similar results in the degree of DNA fragmentation. Furthermore, Biobran + Rad upregulated the relative gene expression and protein level of p53 and Bax in tumor cells, down-regulated Bcl-2 expression, and increased the Bax/Bcl-2 ratio and caspase-3 activity, with the combined treatment greater than for either treatment alone. Additionally, the combined treatment modulated the decrease in body weight, the increase in liver and spleen weight, and the elevation of liver enzymes aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transferase to be within normal values. We conclude that Biobran enhances radiation therapy-induced tumor regression by potentiating apoptosis and minimizing toxicities related to radiation therapy, suggesting that Biobran may be useful in human cancer patients undergoing radiotherapy and warranting clinical trials.


Assuntos
Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/radioterapia , Xilanos/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Peso Corporal/efeitos dos fármacos , Peso Corporal/efeitos da radiação , Carcinoma de Ehrlich/genética , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/efeitos da radiação , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Terapia Combinada , Dano ao DNA , Fragmentação do DNA/efeitos dos fármacos , Fragmentação do DNA/efeitos da radiação , Feminino , Regulação da Expressão Gênica , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologia , Fígado/efeitos da radiação , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Tamanho do Órgão/efeitos da radiação , Baço/efeitos dos fármacos , Baço/patologia , Baço/efeitos da radiação , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/efeitos da radiação , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Raios X , Xilanos/farmacologia , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
6.
World J Gastroenterol ; 25(33): 4850-4869, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31543678

RESUMO

Thirty per cent of all colorectal tumours develop in the rectum. The location of the rectum within the bony pelvis and its proximity to vital structures presents significant therapeutic challenges when considering neoadjuvant options and surgical interventions. Most patients with early rectal cancer can be adequately managed by surgery alone. However, a significant proportion of patients with rectal cancer present with locally advanced disease and will potentially benefit from down staging prior to surgery. Neoadjuvant therapy involves a variety of options including radiotherapy, chemotherapy used alone or in combination. Neoadjuvant radiotherapy in rectal cancer has been shown to be effective in reducing tumour burden in advance of curative surgery. The gold standard surgical rectal cancer management aims to achieve surgical removal of the tumour and all draining lymph nodes, within an intact mesorectal package, in order to minimise local recurrence. It is critically important that all rectal cancer cases are discussed at a multidisciplinary meeting represented by all relevant specialties. Pre-operative staging including CT thorax, abdomen, pelvis to assess for distal disease and magnetic resonance imaging to assess local involvement is essential. Staging radiology and MDT discussion are integral in identifying patients who require neoadjuvant radiotherapy. While Neoadjuvant radiotherapy is potentially beneficial it may also result in morbidity and thus should be reserved for those patients who are at a high risk of local failure, which includes patients with nodal involvement, extramural venous invasion and threatened circumferential margin. The aim of this review is to discuss the role of neoadjuvant radiotherapy in the management of rectal cancer.


Assuntos
Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/epidemiologia , Lesões por Radiação/epidemiologia , Neoplasias Retais/terapia , Carga Tumoral/efeitos da radiação , Intervalo Livre de Doença , Humanos , Excisão de Linfonodo , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Linfonodos/efeitos da radiação , Imagem por Ressonância Magnética , Terapia Neoadjuvante/efeitos adversos , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Órgãos em Risco/efeitos da radiação , Seleção de Pacientes , Cuidados Pré-Operatórios/métodos , Protectomia , Lesões por Radiação/etiologia , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Reto/patologia , Reto/efeitos da radiação , Reto/cirurgia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
7.
Acta Oncol ; 58(10): 1404-1409, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31530120

RESUMO

Purpose: Despite widespread concerns of radiotherapy toxicity in children with head and neck tumors, recent Children's Oncology Group (COG) findings suggest that the use of 45 Gy results in an unacceptably high rate of local recurrences in patients with low-risk orbital rhabdomyosarcoma. We therefore evaluated outcomes in our pediatric patients who received 45 GyRBE using proton therapy. Material and methods: To assess disease control and toxicity, we reviewed the medical records of 30 children (≤21 years old) with COG stage 1, group III embryonal orbital rhabdomyosarcoma enrolled on a prospective outcome study and treated with proton therapy between 2007 and 2018. Results: Median age at the time of radiation was 4.8 years old. Twenty-one and nine patients received ifosfamide- and cyclophosphamide-based chemotherapy according to their respective cooperative group regimens. Median duration between the start of induction chemotherapy and radiation was 12 weeks. Two patients had a complete response to induction chemotherapy and two had stable disease. Twenty-six patients had a partial response to induction chemotherapy, with a median volume reduction of 66%. With a median follow-up of 4.0 years (range, 0.5-9.5 years), we observed 1 local failure 6 months following treatment in a patient who had a partial response to cyclosphophomide-based induction chemotherapy. The 5-year local control, progression-free survival, and overall survival rates were 97%, 97%, and 100%, respectively. Serious late toxicities included 18 patients with cataracts, 4 with exposure keratoconjunctivitis resulting in permanently reduced visual acuity, and 1 with chronic sinusitis. Conclusion: 45 GyRBE offers effective local control for most patients with group III orbital rhabdomyosarcoma. The delivery of proton therapy to the postinduction tumor volume plus a small margin can mitigate early- and intermediate-term toxicity, but side effects still occur and long-term data are needed to demonstrate the dosimetric advantage of proton therapy.


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Neoplasias Orbitárias/terapia , Terapia com Prótons/métodos , Rabdomiossarcoma Embrionário/terapia , Carga Tumoral/efeitos da radiação , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Relação Dose-Resposta à Radiação , Feminino , Seguimentos , Humanos , Ifosfamida/administração & dosagem , Lactente , Masculino , Terapia Neoadjuvante/métodos , Neoplasias Orbitárias/mortalidade , Intervalo Livre de Progressão , Estudos Prospectivos , Terapia com Prótons/efeitos adversos , Planejamento da Radioterapia Assistida por Computador , Rabdomiossarcoma Embrionário/mortalidade , Carga Tumoral/efeitos dos fármacos
8.
Acta Oncol ; 58(10): 1476-1482, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31432722

RESUMO

Introduction: Positron emission tomography (PET) using hypoxia-selective tracers like FAZA may guide radiation dose-escalation approaches. However, poor resolution combined with slow tracer retention in relatively inaccessible target cells and slow clearance of unbound tracer results in low-contrast images, and areas where viable hypoxic tracer retaining cells and necrosis (no tracer) are intermixed may pass unnoticed during image thresholding. Here we hypothesized that a clinical feasible one-day dual tracer approach that combines a short-lived (e.g., 11C labeled) metabolic tracer that provides voxel-wise information on viable tissue volume (preferably independently of tumor microenvironment) and a hypoxia marker, may limit threshold-based errors. Material and methods: 11C-acetate and 11C-methionine uptake was quantified in tumor cell lines under tumor microenvironment-mimicking conditions of high/low O2 (21%/0%) and pH (7.4/6.7). Next, tumor-bearing mice were administered FAZA and sacrificed 1 h (mimics a clinical low-contrast image scenario) or 4 h (high contrast) later. In addition, all mice were administered pimonidazole (hypoxia) and 14C-methionine 1 h prior to sacrifice. Tumor tissue sections were analyzed using dual-tracer autoradiography. Finally, FAZA, or FAZA normalized to 14C-methionine retention (to adjust for differences in viable tissue volume) was compared to hypoxic fraction (deduced from immune-histological analysis of pimonidazole; ground truth) in PET-mimicking macroscopic pixels with variable extent of necrosis/hypoxia. Results/conclusions: Low pH stimulated 11C-acetate retention in many cell lines, and uptake was further modified by anoxia, compromising its usefulness as a universal marker of viable tumor volume. In contrast, 11C-methionine was largely unaffected by the in vitro microenvironment and was further tested in mice. Necrosis increased the risk of missing hypoxia-containing pixels during thresholding and hypoxic fraction and FAZA signal correlated poorly in the low contrast-scenario. Voxel-based normalization to 14C-methionine increased the likelihood of detecting voxels harboring hypoxic cells profoundly, but did not consistently improve the correlation between the density of hypoxic cells and tracer signal.


Assuntos
Neoplasias/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Tolerância a Radiação , Compostos Radiofarmacêuticos/administração & dosagem , Carga Tumoral/efeitos da radiação , Animais , Autorradiografia/métodos , Hipóxia Celular/efeitos da radiação , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Camundongos , Necrose/diagnóstico por imagem , Neoplasias/patologia , Neoplasias/radioterapia , Nitroimidazóis/administração & dosagem , Microambiente Tumoral/efeitos da radiação , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Acta Oncol ; 58(10): 1416-1422, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31364899

RESUMO

Background: Children with brain tumors undergoing radiotherapy are at particular risk of radiation-induced morbidity and are therefore routinely considered for proton therapy (PT) to reduce the dose to healthy tissues. The aim of this study was to apply pediatric constraints and normal tissue complication probability (NTCP) models when evaluating the differences between PT and contemporary photon-based radiotherapy, volumetric modulated arc therapy (VMAT). Methods: Forty patients (aged 1-17 years) referred from Norwegian institutions to cranial PT abroad during 2014-2016 were selected for VMAT re-planning using the original CT sets and target volumes. The VMAT and delivered PT plans were compared by dose/volume metrics and NTCP models related to growth hormone deficiency, auditory toxicity, visual impairment, xerostomia, neurocognitive outcome and secondary brain and parotid gland cancers. Results: The supratentorial brain, temporal lobes, hippocampi, hypothalamus, pituitary glands, cochleas, salivary glands, optic nerves and chiasm received lower mean doses from PT. Reductions in population median NTCP were significant for auditory toxicity (VMAT: 3.8%; PT: 0.3%), neurocognitive outcome (VMAT: 3.0 IQ points decline at 5 years post RT; PT: 2.5 IQ points), xerostomia (VMAT: 2.0%; PT: 0.6%), excess absolute risk of secondary cancer of the brain (VMAT: 9.2%; PT: 6.7%) and salivary glands (VMAT: 2.8%; PT:0.5%). Across all patients, 23/38 PT plans had better or comparable estimated risks for all endpoints (within ±10% of the risk relative to VMAT), whereas for 1/38 patients all estimates were better or comparable with VMAT. Conclusions: PT reduced the volumes of normal tissues exposed to radiation, particularly low-to-intermediate dose levels, and this was reflected in lower NTCP. Of the included endpoints, substantial reductions in population medians were seen from the delivered PT plans for auditory complications, xerostomia, and risk of secondary cancers of the brain and salivary glands.


Assuntos
Neoplasias Encefálicas/radioterapia , Modelos Biológicos , Órgãos em Risco/efeitos da radiação , Terapia com Prótons/efeitos adversos , Lesões por Radiação/epidemiologia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/efeitos adversos , Adolescente , Criança , Pré-Escolar , Relação Dose-Resposta à Radiação , Feminino , Humanos , Lactente , Masculino , Noruega/epidemiologia , Fótons/efeitos adversos , Fótons/uso terapêutico , Probabilidade , Terapia com Prótons/métodos , Lesões por Radiação/etiologia , Lesões por Radiação/prevenção & controle , Radiometria , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Medição de Risco/métodos , Carga Tumoral/efeitos da radiação
11.
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
12.
Acta Oncol ; 58(10): 1386-1392, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31271118

RESUMO

Introduction: We hypothesized that gross tumor volume (GTV) of primary tumor (GTVT) and nodal volumes (GTVN) were predictors of first failure site in non-small cell lung cancer (NSCLC). We aimed at also comparing the prognostic model's complexity to its ability to generate absolute risk predictions with emphasis on variables available at the time of diagnosis. Materials and methods: Three hundred and forty-two patients treated with definitive chemoradiotherapy (CRT) for adenocarcinoma (AC) or squamous cell carcinoma (SCC) in 2009-2017 were analyzed. Clinical data, standardized uptake values on FDG-PET/CT, GTVT and GTVN were analyzed using multivariate competing risk models. Results: One hundred and thirty-seven patients had SCC. As first site of failure 49 had locoregional failure (LRF), 40 had distant metastasis (DM) and 24 died with no evidence of disease (NED). In 205 patients with AC, 34 had LRF, 118 had DM as first failure site and 17 died with NED. Performance status predicted LRF (p = .02) and UICC stage risk of DM (p = .05 for stage 3, p < .001 for stage 4). Adding histopathology changed predictions with much reduced risk of LRF in AC compared to SCC (HR = 0.5, 95% CI: (0.3-0.75), p = .001). Conversely, AC had a higher rate of DM than SCC (HR = 2.1, 95% CI: (1.5-3.0], p < .001). Addition of FDG metrics and tumor/nodal volume data predicted DM risk (p = .001), but with smaller impact on absolute risk compared to histopathology. Separation of GTV in nodal and tumor lesions did not improve risk predictions. Conclusions: We quantified the effect of adding volumetric and quantitative imaging to competing risk models of first failure site, but did not find tumor volume components to be important. Histopathology remains the simplest and most important factor in prognosticating failure patterns in NSCLC.


Assuntos
Adenocarcinoma de Pulmão/terapia , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/métodos , Neoplasias Pulmonares/terapia , Modelos Biológicos , Recidiva Local de Neoplasia/diagnóstico , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Fluordesoxiglucose F18/administração & dosagem , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pulmão/efeitos da radiação , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/prevenção & controle , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Prognóstico , Intervalo Livre de Progressão , Planejamento da Radioterapia Assistida por Computador/métodos , Estudos Retrospectivos , Medição de Risco/métodos , Carga Tumoral/efeitos da radiação
15.
In Vivo ; 33(4): 1203-1208, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31280210

RESUMO

BACKGROUND/AIM: Malignant glioma is a rapidly progressive primary brain cancer. The aim of the study was to investigate the effect of far-infrared ray (FIR) on temozolomide (TMZ)-treated glioma in rats. MATERIALS AND METHODS: Male, 8-week old, Fischer 344 inbred rats with glioma were randomly divided into three study groups (20 rats in each group). The control group received saline only once daily for 5 days. The TMZ group received TMZ (30 mg/kg) once daily for 5 days. The TMZ plus FIR group received TMZ (30 mg/kg) once daily for 5 days and infrared-c irradiation of 40 min twice daily for 4 weeks. The relative tumor fold and the expression of hypoxia-induced factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were compared using one-way ANOVA at the end of study. RESULTS: The relative tumor fold of the TMZ+FIR group was significantly higher compared to the control group, and was borderline higher compared to the TMZ group at Day 7. The relative tumor fold of TMZ+FIR group was significantly higher compared to the control group and the TMZ group at Days 14, 21 and 28. HIF-1α expression of TMZ+FIR group was borderline higher compared to the control group at Day 28. The VEGF expression of TMZ+FIR group was significantly higher compared to the control group and the TMZ group at Day 28. CONCLUSION: FIR might increase the growth of glioma under TMZ treatment in rats possibly via increasing VEGF expression, but not HIF-1α expression.


Assuntos
Antineoplásicos Alquilantes/farmacologia , Glioma/terapia , Raios Infravermelhos , Temozolomida/farmacologia , Animais , Biomarcadores , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Terapia Combinada , Modelos Animais de Doenças , Glioma/metabolismo , Glioma/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Ratos , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/efeitos da radiação , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Diagn Interv Imaging ; 100(11): 699-708, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31257114

RESUMO

PURPOSE: To evaluate the utility of multi-parametric magnetic resonance imaging (MP-MRI), including dynamic contrast-enhanced MRI and diffusion-weighted MRI, for monitoring tumor tissue changes after volumetric-modulated arc radiotherapy in localized prostate cancer (PCa), and to compare the radiotherapy induced tumor tissue changes between conventional, moderate and extreme hypofractionated groups. Furthermore, we aimed to evaluate if follow-up by MRI has an incremental value compared to the standard care by prostate-specific antigen (PSA) serum level measurement. MATERIALS AND METHODS: Fifty-five men (mean age: 70±5 [SD] years; range: 60-79 years) with biopsy-proven PCa underwent MRI examination before radiotherapy, and at 3 and 12 months after radiotherapy. Pharmacokinetic analysis post-processing platform with dedicated software (Tissue 4D) was used to generate colorized parametric maps of enhancing tumors. The volume transfer constant (Ktrans), reflux constant (Kep), and initial area under curve (iAUC) were calculated from the tumors. Tumor apparent diffusion coefficient (ADC) value was measured on the ADC map. The patients were allocated into three radiotherapy groups: 17 conventional (39×2Gy), 16 moderate (20×3Gy) and 22 extreme hypofractionated (5×7.25Gy) regimen. RESULTS: Sixty lesions were detected in the prostates of the 55 patients. Follow-up MRI showed decreases in tumor size and degree of enhancement. Ktrans, Kep, and iAUC all decreased at 3 months (P<0.001, respectively) and decreased further at 12 months (P<0.001, respectively). ADC increased at 3 months (P<0.001) and increased further at 12 months (P<0.001). There were no significant differences in the percentage changes of the measured MP-MRI parameters of the tumors from baseline to 12 months between the conventional, moderate and extreme hypofractionated regimen groups. CONCLUSION: MP-MRI is a reliable tool for lesion detection and follow-up, providing both qualitative and quantitative data.


Assuntos
Imageamento por Ressonância Magnética Multiparamétrica/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Radioterapia de Intensidade Modulada/métodos , Idoso , Área Sob a Curva , Meios de Contraste , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Hipofracionamento da Dose de Radiação , Monitoramento de Radiação/métodos , Carga Tumoral/efeitos da radiação
17.
Ann Nucl Med ; 33(9): 681-688, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31214958

RESUMO

PURPOSE: The primary aim of this study was to evaluate the volumetric therapy response via Ga-68 PSMA I&T PET/CT in patients treated with Lu-177 PSMA I&T therapy. The secondary purpose was to determine the impact of volumetric parameter responses to overall survival. METHODS: PSMA tumor volumes (PSMA-TV) and tumor lesion PSMA expressions (TL-PSMA) were calculated with a semi-automatic program on Ga-68 PSMA I&T PET/CT images that were obtained before and after Lu-177 PSMA I&T therapies with 19 patients. The median overall survival was compared with PSMA-TV, TL-PSMA, SUVmax, PSA, and alteration in PERCIST criteria. RESULTS: PSMA-TV values were decreased in 12 patients (63%), and TL-PSMA values were decreased in 15 patients (79%) following the therapy. The SUVmax and the PSA values were also decreased in 14 (74%) and 10 (53%) patients, respectively. The complete remission (CR) was observed in two patients (10%). The partial response (PR) and progressive disease were observed in 6 (32%) and 11 (58%) patients, respectively, according to PRECIST criteria. The survival rates were statistically significant in patients with a decrease in PSMA-TV and TL-PSMA values than patients without any decrease (p 0.001, p < 0.001, respectively). However, the survival rates did not differ in responders (PR or CR) and non-responders according to the PERCIST criteria (p 0.232). The survival rates did not also differ in responders and non-responders according to the SUVmax and PSA values (p 0.140, p 0.206, respectively). CONCLUSIONS: Molecular and volumetric parameters are beneficial in the assessment of Lu-177 PSMA I&T therapy response. Although the number of patients is small, TL-PSMA response, which includes both the tumor volume and PSMA expression in tumor, may be considered as the most valuable parameter for the evaluation of the therapy response and the prediction of survival rate.


Assuntos
Antígenos de Superfície/metabolismo , Glutamato Carboxipeptidase II/metabolismo , Lutécio/uso terapêutico , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Radioisótopos/uso terapêutico , Idoso , Humanos , Masculino , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Carga Tumoral/efeitos da radiação
18.
Acta Oncol ; 58(10): 1446-1450, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31241385

RESUMO

Background: Proton dose distributions are sensitive to range uncertainties, resulting in margins added to ensure adequate tumor control probability (TCP). We investigated the required margin and dose shape needed to ensure adequate TCP, for representative tumor cell distributions in the clinical target volume (CTV). Material and methods: A mechanistic tumor response model, validated for lung tumors, was used to estimate TCP. The tumor cell distribution ( ρ ) was assumed to decrease exponentially in the CTV with decay parameter λ toward the outer border ( xCTVmax ). It was investigated if a gradual dose fall-off could reduce the dose to normal tissues outside the CTV, while achieving adequate TCP. For various values of xCTVmax and λ, we derived adequate uniform dose margins ( m ), coupled to linear dose fall-off regions ( Δx, Δxnom=Δx-0.9 cm), that ensured TCP>TCPlimit, while delivering the least mean dose outside the CTV. To account for variabilities in patients and tumor types, variable probabilities ( p ) of finding tumor cells in the non-GTV part of the CTV for a given patient were also tested. Dose from a single beam or two opposing beams was simulated under the influence of a typical stopping power ratio uncertainty of 3.5%. Results: For large λ and xCTVmax, a dose distribution with a shallower dose fall-off ( Δx>0 ) was advantageous, and m could be smaller than xCTVmax. In the case of small xCTVmax values, however, a conventional dose distribution ( Δx=0 ) would generally perform better. For no CTV, m=0.4 cm in the case of two opposing beams, while it was 0.7 cm for a single beam, however, for two opposing beams Δx=1.2 cm ( Δxnom=0.3 cm), while it was zero for a single beam. Conclusion: The details of the underlying cancer cell distribution characteristics do impact the adequate dose arrangements, and for opposing beams a non-conventional dose distribution shape is often advantageous.


Assuntos
Neoplasias Pulmonares/radioterapia , Modelos Biológicos , Terapia com Prótons/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Carga Tumoral/efeitos da radiação , Fracionamento da Dose de Radiação , Humanos , Modelagem Computacional Específica para o Paciente , Terapia com Prótons/efeitos adversos , Dosagem Radioterapêutica , Sensibilidade e Especificidade , Incerteza
19.
Nanotechnology ; 30(35): 355101, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31082814

RESUMO

Metallic nanorods are promising agents for a wide range of biomedical applications. We report an optical hyperthermia method capable of inducing slowdown tumor progression of an experimental in vivo CT-2A glioblastoma tumor. The tumor model used in this research is based on the transplantation of mouse astrocytoma CT-2A cells in the striatum of mice by intracranial stereotaxic surgery. Two weeks after cell implant, the resulting tumor is treated by irradiating intratumoral injected gold nanorods, biofunctionalized with CD133 antibody (B-GNRs), using a continuous wave laser. Nanoparticles convert the absorbed light into localized heat (reaching up to 44 °C) due to the effect of surface plasmon resonance. A significant slowdown in CT-2A tumor progression is evident, by histology and magnetic resonance imaging, at one (p = 0.03) and two weeks (p = 0.008) after irradiation treatment. A notable deceleration in tumor size (15%-75%) as compared to the control untreated groups, it is observed. Thus, laser irradiation of B-GNRs is found to be effective for the treatment of CT-2A tumor progression. Similarities between the pre-clinical CT-2A tumor model and the human astrocytoma disease, in terms of anatomy, metastatic behavior and histopathology, suggest that hyperthermic treatment by laser irradiation of B-GNRs administered into high-grade human astrocytoma might constitute a promising alternative treatment to limit the progression of this deadly disease.


Assuntos
Astrocitoma/terapia , Neoplasias Encefálicas/terapia , Ouro/farmacologia , Hipertermia Induzida/métodos , Terapia a Laser/métodos , Nanotubos/química , Antígeno AC133/antagonistas & inibidores , Antígeno AC133/imunologia , Animais , Anticorpos Neutralizantes/farmacologia , Astrocitoma/imunologia , Astrocitoma/patologia , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Progressão da Doença , Ouro/administração & dosagem , Ouro/química , Humanos , Injeções Intralesionais , Lasers , Camundongos , Camundongos Endogâmicos C57BL , Nanotubos/ultraestrutura , Transplante de Neoplasias , Técnicas Estereotáxicas , Ressonância de Plasmônio de Superfície , Carga Tumoral/efeitos da radiação
20.
Cancer Lett ; 457: 1-9, 2019 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-31078733

RESUMO

The tumor microenvironment regulates cancer initiation, progression and response to treatment. In particular, the immature tumor vasculature may impede drugs from reaching tumor cells at a lethal concentration. We and others have shown that radiation therapy (RT) induces pericyte recruitment, resembling vascular normalization. Here, we asked whether radiation-induced vascular remodeling translates into improved tissue distribution and efficacy of chemotherapy. First, RT induced vascular remodeling, accompanied by decreased hypoxia and/or increased Hoechst perfusion in prostate PC3 and LNCaP and Lewis lung carcinoma. These results were independent of the RT regimen, respectively 10 × 2 Gy and 2 × 12 Gy, suggesting a common effect. Next, using doxorubicin as a fluorescent reporter, we observed that RT improves intra-tumoral chemotherapy distribution. These effects were not hindered by anti-angiogenic sunitinib. Moreover, sub-optimal doses of doxorubicin had almost no effect alone, but significantly delayed tumor growth after RT. These data demonstrate that RT favors the efficacy of chemotherapy by improving tissue distribution, and could be an alternative chemosensitizing strategy.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Carcinoma Pulmonar de Lewis/irrigação sanguínea , Carcinoma Pulmonar de Lewis/terapia , Quimiorradioterapia , Doxorrubicina/farmacologia , Neoplasias da Próstata/irrigação sanguínea , Neoplasias da Próstata/terapia , Doses de Radiação , Remodelação Vascular/efeitos da radiação , Animais , Antibióticos Antineoplásicos/metabolismo , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma Pulmonar de Lewis/patologia , Doxorrubicina/metabolismo , Feminino , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Nus , Neovascularização Patológica , Células PC-3 , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Distribuição Tecidual , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/efeitos da radiação , Hipóxia Tumoral , Microambiente Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
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