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1.
Breast ; 49: 41-47, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31677532

RESUMO

PURPOSE: This study evaluated the influence of prognostic factors and whole brain radiotherapy (WBRT) on overall survival (OS) of breast cancer (BC) patients with brain metastases (BM). METHODS AND MATERIALS: Medical records of 730 BC patients diagnosed with BM from 2000 to 2014 at 17 institutions were retrospectively reviewed. OS was calculated from BM diagnosis. Median follow-up duration was 11.9 months (range, 0.1-126.2). RESULTS: Median OS was 15.0 months (95% CI: 14.0-16.9). Patients with different BC-specific graded prognostic assessment (GPA) scores showed significant differences (p < 0.001) in OS. In multivariate analysis, histologic grade 3 (p = 0.014), presence of extracranial metastasis (p < 0.001), the number of BM (>4; p = 0.002), hormone receptor negativity (p = 0.005), HER2-negativity (p = 0.003), and shorter time interval (<30 months) between BC and BM diagnosis (p = 0.007) were associated with inferior OS. By summing the ß-coefficients of variables that were prognostic in multivariate analyses, we developed a prognostic model that stratified patients into low-risk (≤0.673) and high-risk (>0.673) subgroups; the high-risk subgroup had poorer median OS (10.1 months, 95% CI: 7.9-11.9 vs. 21.9 months, 95% CI: 19.5-27.1, p < 0.001). Univariate and multivariate analyses of propensity score-matched patients diagnosed with BM ≥ 30 months after BC diagnosis (n = 389, "late BM") revealed that WBRT-treated patients showed superior OS compared to non-WBRT-treated patients (p = 0.070 and 0.030, respectively). CONCLUSION: Our prognostic model identified high-risk BC patients with BM who might benefit from increased surveillance; if validated, our model could guide treatment selection for such patients. Patients with late BM might benefit from WBRT as initial local treatment.

2.
Medicine (Baltimore) ; 98(40): e17390, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577744

RESUMO

Stereotactic radiosurgery (SRS) is considered the initial treatment for lung cancer patients with small-sized and limited number of brain metastases. The objective of this study was to assess clinical outcomes of SRS treatment using CyberKnife (CK) for recursive partitioning analysis (RPA) class II/III patients with 1 to 3 brain metastases from lung cancer and identify which patients in the high RPA class could benefit from SRS.A total of 48 lung cancer patients who received CK-based SRS for their metastatic brain lesions from 2010 to 2017 were retrospectively analyzed. Radiographic response was evaluated during follow-up period. Overall survival (OS) and intracranial progression-free survival (IPFS) were calculated and prognostic variables associated with OS and IPFS were evaluated.Median follow-up time was 6.6 months. Local control rates at 6 months and 1-year following SRS were 98% and 92%, respectively. The median OS of all patients was 8 months. One-year and 2-year OS rates were 40.8% and 20.9%, respectively. In multivariate analysis, uncontrolled primary disease (P = .01) and Eastern Cooperative Oncology Group performance status of 2 or 3 (P = .001) were independent prognostic factors for inferior OS. These 2 factors were also significantly associated with inferior IPFS. In subgroup analysis according to RPA class, primary disease status was the only prognostic factor, showing statistically significant OS differences in both RPA class II and III (controlled vs uncontrolled: 41.1 vs 12.3 months in RPA class II, P = .03; 26.9 vs 4.1 months in RPA class III, P = .01).Our results indicated that SRS could be an effective treatment option for RPA class II/III patients with brain metastases from lung cancer in the modern treatment era. SRS might be particularly considered for patients with controlled primary disease.


Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Neoplasias Pulmonares/patologia , Radiocirurgia/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
4.
Int J Food Sci ; 2019: 8103480, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31467867

RESUMO

Increased caloric intake and Westernized dietary choices may be contributing toward a recent rising trend of incidences of chronic lifestyle-related diseases. In this study, we evaluated the anticancer properties of Plant Enzyme Validux (PEV) using a mouse model. Five-week-old male C3H mice were randomly distributed into four experimental groups: Control, PEV only, 6Gy irradiation only, and PEV + 6Gy. PEV was orally administered daily at 500 mg/kg for 14 days prior to three rounds of 2Gy irradiation. We focused on the anticancer action and immunostimulatory effects of PEV with and without irradiation. Oncogene suppression was observed after PEV treatment as was an increase in TNF-α, suggesting an antitumor effect. PEV administration also appeared to reduce oxidative stress as evidenced by a decrease in lipid peroxidation. In addition, PEV confirmed radioprotective effect by radical blocking ability by radiation irradiation. Immunological responses to PEV administration were evidenced by an increase in number of total white blood cells and T lymphocytes. Immunotherapy is drawing more and more attention as a treatment for prostate cancer, suggesting that there will be a need for the identification of specific targets for prostate cancer and for more basic research on the genetic aspects of immunotherapy. Thus, PEV may be of use as a radioprotective supplement during radiotherapy for tumor treatment.

5.
Radiat Oncol ; 14(1): 110, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221161

RESUMO

BACKGROUND: Incurable inflammatory breast cancer (IBC) patients occasionally suffer from general symptoms such as breast pain, bleeding, ulceration, and discharge, and thus require palliative radiotherapy (RT). Hypofractionated RT has many advantages in palliative settings, but very few studies on IBC have been conducted. This study was conducted to evaluate the effects of hypofractionated RT on symptomatic IBC patients. METHODS: Twenty-two patients with IBC who underwent hypofractionated palliative RT between 2010 and 2016 were retrospectively analyzed. RT was performed at a total dose of 42.5-55 Gy with 2.5-3 Gy per fraction. The treatment effects were evaluated with respect to symptom improvement, tumor response, and treatment-related toxicity. RESULTS: The main symptoms that the patients complained of before RT were pain, bleeding, and discharge. According to the percentage of symptom relief compared with pre-RT symptoms, the number of patients with < 30, 30-70%, and ≥ 70% were 2 (9.1%), 7 (31.8%), and 13 (59.1%), respectively. Eighteen (81.8%) patients showed tumor response. No patient experienced grade 3 or higher acute or chronic toxicity during a median follow-up period of 13 months. In univariate analysis, symptom type was a significant factor for predicting the degree of symptom relief. Meanwhile, RT field and C-reactive protein increase were significant factors for predicting the incidence of radiation-induced skin toxicity. CONCLUSIONS: Hypofractionated RT could safely and effectively relieve symptoms among incurable symptomatic IBC patients.


Assuntos
Neoplasias Inflamatórias Mamárias/radioterapia , Cuidados Paliativos , Hipofracionamento da Dose de Radiação/normas , Planejamento da Radioterapia Assistida por Computador/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Órgãos em Risco/efeitos da radiação , Prognóstico , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos
6.
J Pathog ; 2019: 3431674, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31110820

RESUMO

Electrochemical treatment (ECT) is a promising new way to induce tumor regression by flowing direct current into the cancer tissue. ECT was applied to different kinds of tumors in clinical studies and showed good results. In addition, basic research has almost not been done in the field of evaluation of efficacy, dose-response, and cytotoxicity. Therefore, the objective is to study the cellular mechanism in the antitumor effect of ECT and to contribute data of basic research of ECT. In the cell-level study, tumor cells (Sarcoma-180, Scc-7, Ehrlich Carcinoma) were studied using ICR mice and C3H mice. In the study group, pH values of control, 10mA × 150secs, 10mA × 300secs, and 10mA × 600secs groups were measured five times each. In histological level studies, ECT was performed on tumors inoculated on the upper part of the right foot of C3H mice. In each group, mice were sacrificed by cervical dislocation 6, 12, and 24 hrs after ECT treatment, and tumors were removed. The excised tumor was fixed in tissue with 10% formalin, and HE staining and apoptosis antibody staining were carried out from the obtained tissue section and observation. In the study at the cellular level, statistically significant differences were observed in all ECT groups in Sarcoma in the tumor growth measurement study compared with the control group. Statistically significant differences were also observed in Scc-7 in all ECT groups compared to the control group. In the intratumoral pH measurement study, there was a statistically significant difference between the anode and the cathode in each group compared to the control group. In the examination at the histological level, microscopic observation of a slide stained with apoptosis antibody with a magnification of 400 times showed that 6hrs after ECT it was stronger and then decreased. By performing ECT, a weak current flows in the living body. As a result, changes in tissue pH, generation of gas, etc. occur. In this study, it was also confirmed that the intratumor pH value becomes strongly acidic on the anode side and strongly alkaline on the cathode side. In addition, this study confirmed the occurrence of gas during treatment of ECT. Changes in the pH and the like cause changes in the environment in the cell, denaturation of proteins, apoptosis, and necrosis. In this study, a significant increase in apoptosis was confirmed in each ECT group compared to the control group. Treatment effects by ECT were also observed in tumor growth measurement studies and tumor weight measurement studies. From these research results, ECT is considered to be effective as a tumor treatment method.

7.
Radiother Oncol ; 133: 125-131, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30935568

RESUMO

PURPOSE: To investigate the prognostic significance of lymphovascular space invasion (LVI) and perineural invasion (PNI) in rectal cancer. METHODS AND MATERIALS: Clinical data of 1,232 stage II-III rectal cancer patients from six tertiary institutions were analyzed. All patients were treated by long-course preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME). Adjuvant systemic chemotherapy was performed for 962 (78.1%) patients according to the multidisciplinary team's decision. Treatment outcomes and prognostic factors were evaluated according to the lymphovascular invasion (LVI) and perineural invasion (PNI) status. RESULTS: Five-year overall survival (OS) and recurrence-free survival (RFS) rates of the entire cohort were 84.1% and 71.1%, respectively. There is a significant difference in 5-year OS among both-absent, LVI+ only, PNI+ only, and both-present groups (89.1% vs. 77.9% vs. 67.6% vs. 56.2%; p < 0.001). RFS at five years was significantly different among both-absent, LVI+ only, PNI+ only, and both-present groups (78.7% vs. 58.7% vs. 44.6% vs. 38.6%; p < 0.001). The 5-year distant failure-free survival (DFFS) rate was also significantly different among four groups (84.6% vs. 61.4% vs. 54.2% vs 48.6%; p < 0.001). Although adjuvant chemotherapy did not affect 5-year DFFS in the entire cohort, adjuvant chemotherapy significantly reduced the distant failure rate in patients with PNI+ patients (44.9% vs. 54.6%, p = 0.048), not LVI+ patients (65.0% vs. 56.1%, p = 0.487). CONCLUSION: Compared to LVI, PNI is a more significant prognostic factor in stage II-III rectal patients treated by preoperative CRT and TME surgery. The status of PNI rather than LVI could be an indicator for identifying patients who could benefit from adjuvant systemic chemotherapy.

8.
PLoS One ; 14(1): e0209998, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30653591

RESUMO

BACKGROUND: Although radical cystectomy is a standard treatment in muscle-invasive bladder cancer, bladder preservation therapy including transurethral resection of bladder tumor, radiotherapy, and concurrent chemotherapy has been widely adopted, recently. This retrospective analysis was performed to evaluate the survival rates and prognostic factors related to treatment outcomes following bladder-preserving therapy including radiotherapy (RT) in bladder cancer with a curative intent. MATERIALS AND METHODS: We conducted a multi-institutional retrospective study of 152 patients with stage II-IV bladder cancer treated with curative RT between 2000 and 2010. There were 72 patients in stage II, 49 in stage III, and 31 in stage IV. Ninety-seven patients were treated with concurrent chemoradiotherapy and fifty-five with RT alone. Radiation was delivered to the pelvis (median 63 Gy), mainly with cisplatin. The median follow-up time was 35.5 months. RESULTS: Sixty-nine patients (45.4%) showed a complete response to RT. The 5-year overall survival (OS) rate was 45.8%, the 5-year cause-specific survival (CSS) rate was 48.9%, and the 5-year disease-free survival (DFS) rate was 20.8%. Univariate analysis revealed significant differences in the following factors according to the survival rates: patient age, initial hemoglobin level, clinical T stage, clinical N stage, clinical stage group, tumor response to RT, hydronephrosis, and concurrent chemotherapy. Multivariate analysis also revealed a significant difference in patient age (p = 0.003 in OS, p<0.017 in CSS) and tumor response to RT (p = 0.002 in OS, p<0.001 in CSS). Concurrent chemotherapy was significantly different in the DFS rates (p = 0.046). CONCLUSIONS: The survival rates reported herein are comparable to those from other studies, and tumor response and concurrent chemoradiotherapy were significant prognostic factors for better survival rates. Further randomized studies are needed to elucidate the impact of RT in bladder cancer.


Assuntos
Neoplasias da Bexiga Urinária/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , República da Coreia/epidemiologia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Bexiga Urinária/patologia , Bexiga Urinária/efeitos da radiação , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/radioterapia
9.
Tumori ; 105(5): 434-440, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30117371

RESUMO

PURPOSE: There is uncertainty over the effect of systemic inflammatory response on oncologic outcomes in patients who underwent neoadjuvant chemoradiotherapy and surgery for rectal cancer. We investigated the association between neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) as markers of systemic inflammation and tumor response and prognosis after treatment. METHODS: A total of 176 patients who underwent neoadjuvant chemoradiotherapy and curative surgery for rectal cancer were analyzed retrospectively. Pretreatment hematologic parameters and the main clinical factors for patients and tumors were investigated with respect to their relationship with tumor regression and survival. RESULTS: In the receiver operating characteristic analysis, NLR 2.0 and PLR 133.4 had the highest sensitivity and specificity in predicting tumor response. NLR <2.0 and PLR <133.4 were significantly correlated with good tumor response (odds ratio [OR] 2.490, 95% confidence interval [CI] 1.264-4.904, p = .008; OR 3.009, 95% CI 1.477-6.127, p < .001). Patients with NLR <2.0 had significantly better 5-year disease-free survival rate and overall survival rate compared to patients with NLR ⩾2.0 in multivariate analysis (86.8% vs 70.7%, p = .014; 92.4% vs 71.9%, p = .027). CONCLUSIONS: Elevated NLR and PLR levels can be considered as predictors of poor pathologic response, and NLR can be considered a prognosticator in patients who underwent neoadjuvant chemoradiotherapy for locally advanced rectal cancer.


Assuntos
Prognóstico , Neoplasias Retais/sangue , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Adulto , Idoso , Quimiorradioterapia/efeitos adversos , Feminino , Humanos , Linfócitos/efeitos dos fármacos , Linfócitos/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Neutrófilos/efeitos dos fármacos , Neutrófilos/efeitos da radiação , Neoplasias Retais/patologia
10.
Oncol Rep ; 40(6): 3752-3762, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30272295

RESUMO

Previous studies suggest that cancer stem cells (CSCs) exist in solid tumors, and contribute to therapeutic resistance and disease recurrence. Therefore, the present study aimed to investigate whether radioresistant (RT­R) breast cancer cells derived from breast cancer cells increase the number of CSCs, and whether these CSCs are responsible to increased invasiveness and therapeutic resistance. MCF­7, T47D and MDA­MB­231 cells were irradiated 25 times (2 Gy each; 50 Gy total) to generate radioresistant breast cancer cells (RT­R­MCF­7, RT­R­T47D and RT­R­MDA­MB­231). RT­R­breast cancer cells demonstrated increased cell viability against irradiation and increased colony forming abilities compared with parental breast cancer cells. Particularly, RT­R­MDA­MB­231 cells derived from highly metastatic MDA­MB­231 cells exhibited most radioresistance and chemoresistance of the three cell lines. In addition, MDA­MB­231 cells exhibited the most increased protein levels of CSCs markers cluster of differentiation 44, Notch­4, octamer­binding transcription factor 3/4 and aldehyde dehydrogenase 1, compared with RT­R­MCF­7 cells, suggesting highly metastatic breast cancer cells MDA­MB­231 produce more CSCs. RT­R­MDA­MB­231 cells increased intercellular adhesion molecule­1 and vascular cell adhesion molecule­1 levels, resulting in enhanced migration and adhesion to endothelial cells (ECs), and enhanced invasiveness through ECs by inducing matrix metalloproteinase­9, Snail­1 and ß­catenin, and by downregulating E­cadherin compared with MDA­MB­231 cells. These results suggest that highly metastatic breast cancer cells may increase the number of CSCs following radiation therapy, and CSCs present in RT­R­MDA­MB­231 cells contribute to the enhanced invasiveness by increasing migration, adhesion to ECs and invasion through ECs by promoting epithelial­mesenchymal transition (EMT) via the upregulation of adhesion molecules and EMT­associated proteins.


Assuntos
Neoplasias da Mama/metabolismo , Resistencia a Medicamentos Antineoplásicos , Células-Tronco Neoplásicas/metabolismo , Tolerância a Radiação , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Adesão Celular , Linhagem Celular Tumoral , Sobrevivência Celular , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos da radiação , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Células MCF-7 , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/efeitos da radiação , Regulação para Cima
11.
Thorac Cancer ; 9(12): 1671-1679, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30298701

RESUMO

BACKGROUND: We compared the treatment outcomes of stereotactic body radiotherapy (SBRT) and metastasectomy in patients with pulmonary metastases. METHODS: Twenty-one patients received SBRT (total radiation doses 60 Gy in 3 fractions or 48 Gy in 4 fractions) and 30 underwent metastasectomy, most (93.3%) with wedge resection. The patients were followed for a median of 13.7 months. The tumor size in the SBRT group was larger than in the metastasectomy group (median 2.5 vs. 1.25 cm; P = 0.015). Patients with synchronous metastases were more likely to be treated with SBRT than with metastasectomy (P = 0.006). RESULTS: There was no significant difference in the local control rates of the treatment groups (P = 0.163). Progression-free survival (PFS) was longer in the metastasectomy than in the SBRT group (P = 0.02), with one and two-year PFS rates of 51.1% and 46% versus 23.8% and 11.9%, respectively. The one and two-year overall survival (OS) rates were 95% and 81.8% in the metastasectomy group and 79.5% and 68.2%, in the SBRT group, respectively. In multivariate analysis, synchronous metastasis was related to poor PFS, and tumor size was the most significant factor affecting OS. There were no significant differences in PFS and OS between treatment groups after dividing patients according to the presence or absence of synchronous metastases. CONCLUSIONS: SBRT is considered a suitable local modality against pulmonary metastases; however, patients with synchronous metastases are only likely to obtain a small benefit from local treatment with either SBRT or surgery.


Assuntos
Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Metastasectomia , Radiocirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Metastasectomia/efeitos adversos , Metastasectomia/métodos , Pessoa de Meia-Idade , Prognóstico , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Dosagem Radioterapêutica , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Carga Tumoral
12.
J Korean Med Sci ; 33(18): e135, 2018 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-29713255

RESUMO

Background: Although intracavitary radiotherapy (ICR) is essential for the radiation therapy of cervical cancer, few institutions in Korea perform 3-dimensional (3D)-based ICR. To identify patients who would benefit from 3D-based ICR, dosimetric parameters for tumor targets and organs at risk (OARs) were compared between 2-dimensional (2D)- and 3D-based ICR. Methods: Twenty patients with locally advanced cervical cancer who underwent external beam radiation therapy (EBRT) following 3D-based ICR were retrospectively evaluated. New 2D-based plans based on the Manchester system were developed. Tumor size was measured by magnetic resonance imaging. Results: The mean high risk clinical target volume (HR-CTV) D90 value was about 10% lower for 2D- than for 3D-based plans (88.4% vs. 97.7%; P = 0.068). Tumor coverage did not differ between 2D- and 3D-based plans in patients with tumors ≤ 4 cm at the time of brachytherapy, but the mean HR-CTV D90 values in patients with tumors > 4 cm were significantly higher for 3D-based plans than for 2D-based plans (96.0% vs. 78.1%; P = 0.017). Similar results were found for patients with tumors > 5 cm initially. Other dosimetric parameters for OARs were similar between 2D- and 3D-based plans, except that mean sigmoid D2cc was higher for 2D- than for 3D-based plans (67.5% vs. 58.8%; P = 0.043). Conclusion: These findings indicate that 3D-based ICR plans improve tumor coverage while satisfying the dose constraints for OARs. 3D-based ICR should be considered in patients with tumors > 4 cm size at the time of brachytherapy or > 5 cm initially.


Assuntos
Imagem Tridimensional , Planejamento da Radioterapia Assistida por Computador , Neoplasias do Colo do Útero/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia , Feminino , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Órgãos em Risco/efeitos da radiação , Dosagem Radioterapêutica , Estudos Retrospectivos , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/patologia
13.
Radiat Oncol ; 13(1): 85, 2018 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-29739420

RESUMO

BACKGROUND: The role of adjuvant radiotherapy (RT) and setting proper RT target volumes have not been clearly demonstrated for extrahepatic bile duct (EHBD) cancer, due to the rarity of the disease and the lack of randomized trials. This study was conducted to evaluate the indication and treatment volume for adjuvant RT in EHBD cancer patients by identifying the prognostic factors for loco-regional (LR) failure, and analyze the patterns of LR failure. METHODS: Ninety-three patients with EHBD cancer, who underwent resection without adjuvant RT, at 2 medical centers, between 2001 and 2016, were analyzed retrospectively. Univariable and multivariable analyses were performed to find the prognostic factors for LR recurrence. The initial patterns of failure were recorded, especially those of LR recurrence, and categorized according to the Japanese classification. RESULTS: The median follow-up duration was 30 months, and 38 (40.9%) patients experienced LR recurrence during this period. With regards to LR recurrence, close or positive resection margin (RM) status (p < 0.001) remained statistically significant in the multivariable analysis. The most common LR recurrence sites were the tumor bed (18.3%), and lymph node (LN) stations No. 8 (14.1%), No. 9 (12.7%), No. 12 (12.7%), No. 13 (5.6%), No. 14 (21.1%), No. 16 (14.1%), and No. 17 (1.4%). CONCLUSIONS: A close or positive RM status may be suggestive of high LR recurrence rates. In such cases, adjuvant RT may improve outcomes. When adjuvant RT is performed, the treatment volume should be well-designed so as to encompass the tumor bed, as well as LN stations No. 8, No. 9, No. 12, No. 14, and No. 16.


Assuntos
Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Extra-Hepáticos/patologia , Recidiva Local de Neoplasia/patologia , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Adjuvante/normas , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Extra-Hepáticos/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Dosagem Radioterapêutica , Estudos Retrospectivos , Fatores de Risco , Falha de Tratamento
14.
J Korean Med Sci ; 33(14): e107, 2018 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-29607633

RESUMO

BACKGROUND: To analyze clinical outcome of CyberKnife (CK) tumor-tracking stereotactic body radiotherapy (SBRT) for prostate cancer (Pca) according to the magnitude of intra-fractional prostate motion. METHODS: Medical records and daily treatment logs for 71 patients who received CK tumor-tracking SBRT were retrospectively analyzed. Statistical relationships between prostate motion and various outcome results, including local recurrence (LR), biochemical failure (BF), and treatment-related toxicity, were investigated in order to evaluate motion-dependent efficacy of tumor-tracking SBRT for Pca. RESULTS: In a total 71 patients, 3 (4.2%) patients with LR, 12 (16.9%) patients with BF, and 22 (31%) patients with grade-II or worse toxicities to rectal or bladder (22 to rectal, 22 to bladder and 8 patients to both) were observed in a median follow-up of 47 months. Magnitudes of intra-fractional tumor motion along superior-inferior, right-left, and anterior-posterior (AP) axes were 0.15 ± 0.31, 0.12 ± 0.19, and 0.73 ± 0.32 mm, respectively. Radial magnitude was estimated to be 1.0 ± 0.35 mm. Intra-fractional movement was not significantly correlated with tumor control. However, it was significant correlated with the incidence of grade-II or worse toxicity to rectum or bladder particularly when tumor motion was in the AP axis. CONCLUSION: Our quantitative results revealed that toxicity related to SBRT treatment was highly sensitive to intra-fractional prostate movements, although local-tumor control was not affected by such movements. Our results demonstrate that precise motion correction is essential in prostate SBRT, even if it seems to be small.


Assuntos
Neoplasias da Próstata/radioterapia , Radiocirurgia/métodos , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Próstata/diagnóstico por imagem , Próstata/fisiologia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Curva ROC , Lesões por Radiação/etiologia , Reto/patologia , Reto/efeitos da radiação , Estudos Retrospectivos , Taxa de Sobrevida , Bexiga Urinária/patologia , Bexiga Urinária/efeitos da radiação
15.
Toxicol Res ; 34(1): 55-63, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29372002

RESUMO

As a part of general toxicity studies of Enterococcus Faecalis 2001 (EF 2001) prepared using heat-treatment bacillus mort body EF 2001 in mice, this study examined the toxicity of EF 2001 in single and repeated administrations following the previous report in order to apply this product to preventive medicine. The safety of oral ingestion of EF 2001 was examined in 6-week-old male and female ICR mice with 1,000 mg/kg, 3,000 mg/kg and 5,000 mg/kg body weight/day administrated by gavage of the maximum acceptable dose of EF 2001. The study was conducted using distilled water as a control following the methods for general toxicity studies described in the "Guidelines for Non-clinical Studies of Pharmaceutical Products 2002". As a control, 1) observation of general conditions, 2) measurement of body weight, 3) determination of food consumption, 4) determination of water consumption, 5) blood test and urinalysis and 6) pathological examination were performed for the administration of EF 2001. Mice received EF 2001 for 13 weeks and results were compared with those of the control group that received distilled water. The results of the above examinations revealed no significant differences between control and EF 2001 groups for both males and females. Thus, no notable toxicity was confirmed with single and repeated oral administrations of EF 2001. Oral administration in the above doses did not result in abnormal symptoms or death during the observation period. No abnormalities in blood cell count or organ weights were seen. Without any evidence of toxicity to cells and organs, EF 2001 is speculated to not adversely affect living organisms. The 50% lethal dose of EF 2001 with oral administration in mice is estimated to be greater than 5,000 mg/kg body weight/day for both male and female mice. Therefore, LD50 value for animals was 5,000 mg/kg or more.

16.
Clin Respir J ; 12(3): 1264-1273, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28618180

RESUMO

OBJECTIVES: To identify the factors that predict the progression of radiological radiation pneumonitis (RP) to symptomatic RP, and to evaluate the usefulness of the neutrophil-lymphocyte ratio (NLR) as a marker of RP severity and prognosis in stage III non-small cell lung cancer (NSCLC) patients treated with definitive concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: We retrospectively reviewed 61 patients treated between January 2010 and December 2015. Patients' demographic characteristics, clinical data, laboratory findings and treatment parameters were analyzed to determine the predictive factors associated with progression from radiological RP to symptomatic RP. RESULTS: Forty-seven patients (77%) exhibited radiological RP at a median of 78 days after radiation therapy (RT) completion, and 15 (32%) of these patients developed symptomatic RP. The interval between RT completion and radiological RP presentation was shorter in patients who progressed to symptomatic RP (P = .001); progression was highly probable if this latency period was ≤2 months (P = .002). Stage and RT technique correlated with symptomatic RP development (P = .046 and P = .046, respectively). Among dosimetric factors, a V20 (defined as the lung volume receiving ≥20 Gy) of >30% was the most significant predictor of symptomatic RP (P = .001). The NLR and C-reactive protein level at radiological RP were higher in patients who developed symptomatic RP (P = .067 and P = .012, respectively). On multivariate analysis, a V20 >30% and an NLR at radiological RP >6 were associated with symptomatic RP development. CONCLUSION: The NLR at radiological RP is a useful biomarker for predicting symptomatic RP development after CCRT in stage III NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Linfócitos/citologia , Neutrófilos/citologia , Lesões por Radiação/sangue , Pneumonite por Radiação/sangue , Planejamento da Radioterapia Assistida por Computador/métodos , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Quimiorradioterapia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Prognóstico , Lesões por Radiação/etiologia , Pneumonite por Radiação/diagnóstico , Pneumonite por Radiação/etiologia , Estudos Retrospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios X
17.
Asia Pac J Clin Oncol ; 14(2): e21-e28, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28589647

RESUMO

AIM: This study aimed to determine predictive values for volumetric measures in patients with oropharyngeal cancer who received definitive chemoradiotherapy (CCRT). METHODS: Contrast-enhanced computed tomography (CT) scans were obtained before radiotherapy (RT) (I), after delivering a median RT of 50.6 Gy (R) and three months after RT (F). Primary site gross tumor volumes (GTV) were assessed using these scans (GTVI , GTVR and GTVF ). The percentage volume change between GTVI and GTVR (GTV change) was calculated. Volumetric analyses of primary site local control (LC) and progression-free survival (PFS) were performed. RESULTS: In total, 35 patients were evaluated, with a median 31 months of follow-up. The 2-year LC rates (LCRs) were 95.0% for patients with GTVI <23 cc, and 42.9% for those with GTVI ≥23 cc (P = 0.001); the 2-year PFS rates were 85.9% and 21.9% (P = 0.002), respectively. Using GTVR classifications <11 cc or ≥11 cc, log-rank tests demonstrated differences in 2-year LCR (95.2% vs 33.3%, P < 0.001) and 2-year PFS (86.5% vs 0%, P < 0.001). There was no local progression in patients with GTV change ≥75%, and GTV change predicted poor PFS (P = 0.026). On multivariate analysis, GTVR ≥11 cc was a significant predictor of poor LCR (hazard ratio [HR] = 26, P = 0.009) and PFS (HR = 8.33, P = 0.046). CONCLUSION: For patients with oropharyngeal cancer treated with definitive CCRT, GTVI , GTVR and GTV changes predicted LC and PFS; GTVR was the most significant predictor of LC and PFS. RT intensification should be considered for patients with larger remaining tumors after CCRT.


Assuntos
Quimiorradioterapia/métodos , Tomografia Computadorizada de Feixe Cônico/métodos , Neoplasias Orofaríngeas/radioterapia , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/patologia , Prognóstico , Resultado do Tratamento
18.
J Cancer ; 8(19): 4155-4161, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29187892

RESUMO

The definition and criteria of radiation-induced hepatic toxicity (RIHT) in hepatocellular carcinoma patients vary among studies. Therefore, the reported rates of RIHT differ among studies, and this causes confusion. In this study, we evaluated RIHT using several laboratory and clinical parameters, and analyzed which criterion is more correlated with RT and survival. Forty-five HCC patients treated with stereotactic body radiotherapy were included for the analysis. All patients had unresectable HCC and Child-Pugh (CP) class A or B baseline liver function. A median total dose of 45 Gy was delivered by CyberKnife in 3 fractions. For individual laboratory parameter, ≥ grade 2 toxicity development of bilirubin, albumin, or prothrombin time by Common Terminology Criteria of Adverse Effects (CTCAE) was correlated with mean liver dose and survival. However, serum transaminases had no correlation with liver mean dose and survival, and were rather affected by other local treatments. Compared to the CTCAE, the increase in the CP score of 2 points or more was better correlated with liver failure and overall survival, and it was not affected by other local treatments or tumor progression. We concluded RIHT was better defined by the change in the CP score rather than the CTCAE in patients treated by stereotactic body radiotherapy for HCC.

19.
Oncotarget ; 8(42): 72739-72747, 2017 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-29069822

RESUMO

PURPOSE: Radiotherapy is currently one of the main treatment modalities for head and neck cancer; however, it also results in severe toxicity to the normal tissue, to the detriment of patients. This study aimed to investigate whether alpha lipoic acid (ALA) could protect against radiation-induced oral mucositis in a rat model. RESULTS: On post-irradiation days 4 and 7, the epithelial layer on oral mucosa showed pronounced injury (shortening of the layer) and it is diminished by ALA pretreatment before radiation. Hif-1a expression was significantly induced in the radiation group on days 4, 7, and 28. GLUT1 expression was also induced by radiation at all time points, and the expression levels peaked on day 28. Phosphorylated p53 level was significantly higher in the radiation group on days 4 and 7, and Bax protein expression was significantly higher in the same group on day 4 than ALA-pretreated radiation group. TUNEL-positive staining was significantly lower in the ALA-pretreated radiation group. MATERIALS AND METHODS: Rats were assigned to one of the following four groups: control, ALA only (100 mg/kg, i.p.), irradiated, and ALA administered 24 h and 30 min prior to irradiation, with the neck area including the oral mucosa evenly irradiated with 2 Gy per minute (total dose, 18 Gy) using a photon 6-MV linear accelerator. Rats were sacrificed 4, 7, 28, or 56 days after radiation. CONCLUSIONS: The results show that ALA can be used to ameliorate radiation-induced oral mucositis with head and neck cancer.

20.
Curr Pharm Biotechnol ; 18(8): 653-661, 2017 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-28969561

RESUMO

BACKGROUND: Enterococcus faecalis 2001 is a probiotic lactic acid bacterium and has been used as a biological response modifier (BRM). From physiological limitation of bacterial preservation in storage and safety, the live E. faecalis 2001 has been heat-treated and the BRM components containing high level of ß-glucan, named EF-2001, were prepared. METHOD: The heat-treated EF-2001 has been examined for the antioxidative potential for radical scavenging and anti-tumor activities as well as immune-enhancing response in mice. Lymphocyte versus polymorphonuclear leukocyte ratio was increased in mice upon treatment with EF-2001. The number of lymphocytes was increased in the EF-2001-treated group. In the mice bearing two different Ehrlich solid and Sarcoma-180 carcinomas, the treatment with EF-2001 resulted in anti-tumor action. Tumor-suppressive capacity upon treatment with EF-2001 was significantly increased compared to normal controls. RESULTS: During the time interval administration of 5 weeks between the priming and secondary administration of EF-2001, the expression and production levels of TNF-α were also observed in the EF- 2001-administered mice. Additionally, anti-tumor activity examined with the intravenous administration of EF 2001 with a 34 times interval was also observed, as the growth of Sarcoma180 cells was clearly inhibited by the EF-2001. CONCLUSION: From the results, it was suggested that the immune response is enhanced due to antioxidative activity caused by the EF-2001 and anti-tumor activity by NK cells and TNF-α.


Assuntos
Antineoplásicos/farmacologia , Enterococcus faecalis , Fatores Imunológicos/farmacologia , Linfócitos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , beta-Glucanas/farmacologia , Animais , Antineoplásicos/isolamento & purificação , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/imunologia , Fatores Imunológicos/isolamento & purificação , Células Matadoras Naturais/efeitos dos fármacos , Linfócitos/imunologia , Macrófagos/imunologia , Masculino , Camundongos Endogâmicos ICR , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Probióticos , Sarcoma 180/tratamento farmacológico , Sarcoma 180/imunologia , Fator de Necrose Tumoral alfa/análise , beta-Glucanas/isolamento & purificação
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