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1.
Cancer Radiother ; 23(6-7): 496-499, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31471251

RESUMO

Stereotactic radiotherapy of oligometastases, mono- or hypofractionated, represents a fundamental change in the practice of the specialty as it was developed for a century. Despite the great heterogeneity of sites, techniques, and doses, most studies found a high local control rate, around 70 to 90% at 2 years, and reduced toxicity, around 5% of grade 3 at 2 years. Four main phase II and III trials are underway in France. Future research concerns the association of stereotactic radiotherapy with immunotherapy or different conventional chemotherapy protocols, the identification of the best clinical presentations, and optimization of fractionation and biological dose for poor prognosis localizations.


Assuntos
Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Neoplasias/radioterapia , Radiocirurgia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/radioterapia , Terapia Combinada/métodos , Previsões , França , Humanos , Imunoterapia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Masculino , Metástase Neoplásica , Neoplasias/patologia , Neoplasias/terapia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia
2.
Gan To Kagaku Ryoho ; 46(4): 705-708, 2019 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-31164511

RESUMO

Primary small bowel cancer is a rare entity; thus, it is often found in progress. Therefore, the prognosis is often poor. Because of its low frequency, there are few reports concerning the treatment for small bowel cancer; hence, it is important to examine individual cases in detail. In this study, we present a case of recurrent small bowel cancer that successfully responded to chemoradiation therapy. Case: A 48-year-old woman had anemia. Colonoscopy showed a tumor in the terminal ileum. Because of invasion in the ovaries and uterus, ileocecal resection, hysterectomy, and bilateral adnexectomy were performed. The pathological diagnosis was small bowel cancer with lymph node metastasis, and CapeOX therapy was administered as postoperative adjuvant chemotherapy. Since local recurrence was detected in the right lower quadrant 6 months after the surgery, IRIS plus BV was initiated. Radiation therapy(2Gy×25 times, total 50 Gy)was also administered within the same period(only S-1 administration during radiation). After radiation therapy, the tumor decreased significantly in size and showed CR. Currently, the patient is under observation without treatment, but she has had no recurrence for 6 years after the confirmation of recurrence(6 years and 6 months after surgery). It is extremely rare for chemoradiation therapy to be effective for recurrent small bowel cancer; we report such a case with literatures.


Assuntos
Neoplasias Colorretais , Neoplasias do Íleo , Quimiorradioterapia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/radioterapia , Feminino , Humanos , Neoplasias do Íleo/tratamento farmacológico , Neoplasias do Íleo/radioterapia , Metástase Linfática , Pessoa de Meia-Idade , Recidiva Local de Neoplasia
3.
Anticancer Res ; 39(5): 2569-2574, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31092454

RESUMO

BACKGROUND/AIM: Existing survival scores for patients with brain metastases were created in heterogeneously treated cohorts. A new score was developed in 56 patients with brain metastases from colorectal cancer treated with 10×3 Gy of whole-brain radiotherapy (WBRT). PATIENTS AND METHODS: Factors found significantly associated with survival (p<0.05) or showing a trend (p<0.08) were included in the tool. The new WBRT-30-CRC was compared to diagnosis-specific graded prognostic assessment (DS-GPA) classification for gastrointestinal cancers. RESULTS: The WBRT-30-CRC included four prognostic groups: 3-4, 5-6, 7-9 and 10 points. Six-month survival rates were 0%, 15%, 38% and 80%. PPV of the 3-4 points-group predicting death ≤6 months was 100% (91% for DS-GPA of 0.0-1.0). PPV of the 10 points-group predicting survival ≥6 months was 80% (0% DS-GPA of 3.5-4.0, 33% DS-GPA of 3.0-4.0). CONCLUSION: The WBRT-30-CRC appeared very precise in identifying patients with brain metastases from colorectal cancer dying ≤6 months or surviving ≥6 months.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Colorretais/radioterapia , Irradiação Craniana , Prognóstico , Adulto , Idoso , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/secundário , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Radiocirurgia , Resultado do Tratamento
4.
Mol Carcinog ; 58(8): 1400-1409, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31020708

RESUMO

We previously reported that ionizing radiation (IR) mediates cell death through the induction of CUGBP elav-like family member 2 (CELF2), a tumor suppressor. CELF2 is an RNA binding protein that modulates mRNA stability and translation. Since IR induces autophagy, we hypothesized that CELF2 regulates autophagy-mediated colorectal cancer (CRC) cell death. For clinical relevance, we determined CELF2 levels in The Cancer Genome Atlas (TCGA). Role of CELF2 in radiation response was carried out in CRC cell lines by immunoblotting, immunofluorescence, autophagic vacuole analyses, RNA stability assay, quantitative polymerase chain reaction and electron microscopy. In vivo studies were performed in a xenograft tumor model. TCGA analyses demonstrated that compared to normal tissue, CELF2 is expressed at significantly lower levels in CRC, and is associated with better overall 5-year survival in patients receiving radiation. Mechanistically, CELF2 increased levels of critical components of the autophagy cascade including Beclin-1, ATG5, and ATG12 by modulating mRNA stability. CELF2 also increased autophagic flux in CRC. IR significantly induced autophagy in CRC which correlates with increased levels of CELF2 and autophagy associated proteins. Silencing CELF2 with siRNA, mitigated IR induced autophagy. Moreover, knockdown of CELF2 in vivo conferred tumor resistance to IR. These studies elucidate an unrecognized role for CELF2 in inducing autophagy and potentiating the effects of radiotherapy in CRC.


Assuntos
Autofagia/fisiologia , Proteínas CELF/metabolismo , Sobrevivência Celular/efeitos da radiação , Neoplasias Colorretais/patologia , Neoplasias Colorretais/radioterapia , Proteínas do Tecido Nervoso/metabolismo , Animais , Proteína 12 Relacionada à Autofagia/metabolismo , Proteína 5 Relacionada à Autofagia/metabolismo , Proteína Beclina-1/metabolismo , Proteínas CELF/genética , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Células HCT116 , Humanos , Masculino , Camundongos , Transplante de Neoplasias , Proteínas do Tecido Nervoso/genética , Prognóstico , Interferência de RNA , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Radiação Ionizante , Transplante Heterólogo
5.
Medicine (Baltimore) ; 98(13): e14135, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30921175

RESUMO

BACKGROUND: Combination therapy based on epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is an emerging trend in cancer treatment, but the clinical value of EGFR-TKIs combination therapy remains controversial. Thus, we conducted a comprehensive analysis of randomized controlled trials (RCTs) comparing EGFR-TKIs combination therapies with monotherapies, aiming to evaluate the safety and efficacy of EGFR-TKIs based combination therapy and to find a more beneficial combination strategy. METHODS: We searched for clinical studies that evaluated EGFR-TKIs combination therapy in cancer. We extracted data from these studies to evaluate the relative risk (RR) of overall response rate (ORR) and grade 3/4 treatment-related adverse events (AEs), the hazard ratios (HRs) of overall survival (OS), and progression-free survival (PFS). RESULTS: Fourteen RCTs were identified (n = 3774). Treatments included combinations of EGFR-TKIs and chemotherapy, combinations of EGFR-TKIs and radiotherapy, and combinations of EGFR-TKIs and bevacizumab. EGFR-TKIs combination therapies showed higher ORR [RR: 1.62; 95% confidence interval (95% CI):1.16-2.26; P = .005], PFS (HR: 0.76; 95% CI: 0.64-0.89; P = .001), and OS (HR: 0.88; 95% CI: 0.79-0.97; P = .013) values than monotherapies. However, higher grade 3/4 treatment-related AEs (RR: 1.79; 95% CI: 1.02-3.15; P = .000) were observed in combination therapy than in monotherapy. CONCLUSION: Our pooled analysis and subgroup analysis results showed that the addition of chemotherapy to EGFR-TKIs better benefits PFS and safety. Adding bevacizumab was associated with better ORR and OS. The efficacy and safety of a bevacizumab-EGFR-TKIs-chemotherapy combination should be investigated further.


Assuntos
Bevacizumab/farmacologia , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Bevacizumab/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/radioterapia , Intervalo Livre de Doença , Tratamento Farmacológico/métodos , Cloridrato de Erlotinib/administração & dosagem , Cloridrato de Erlotinib/farmacologia , Gefitinibe/administração & dosagem , Gefitinibe/farmacologia , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Radioterapia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
BMC Cancer ; 19(1): 173, 2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30808323

RESUMO

BACKGROUND: The aim of this analysis was to model the effect of local control (LC) on overall survival (OS) in patients treated with stereotactic body radiotherapy (SBRT) for liver or lung metastases from colorectal cancer. METHODS: The analysis is based on pooled data from two retrospective SBRT databases for pulmonary and hepatic metastases from 27 centers from Germany and Switzerland. Only patients with metastases from colorectal cancer were considered to avoid histology as a confounding factor. An illness-death model was employed to model the relationship between LC and OS. RESULTS: Three hundred eighty-eight patients with 500 metastatic lesions (lung n = 209, liver n = 291) were included and analyzed. Median follow-up time for local recurrence assessment was 12.1 months. Ninety-nine patients with 112 lesions experienced local failure. Seventy-one of these patients died after local failure. Median survival time was 27.9 months in all patients and 25.4 months versus 30.6 months in patients with and without local failure after SBRT. The baseline risk of death after local failure exceeds the baseline risk of death without local failure at 10 months indicating better survival with LC. CONCLUSION: In CRC patients with lung or liver metastases, our findings suggest improved long-term OS by achieving metastatic disease control using SBRT in patients with a projected OS estimate of > 12 months.


Assuntos
Neoplasias Colorretais/radioterapia , Neoplasias Hepáticas/radioterapia , Neoplasias Pulmonares/radioterapia , Radiocirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/secundário , Bases de Dados Factuais , Feminino , Seguimentos , Alemanha , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Análise de Sobrevida , Suíça , Resultado do Tratamento , Adulto Jovem
8.
Rev. chil. cir ; 71(1): 55-60, feb. 2019. tab
Artigo em Espanhol | LILACS | ID: biblio-985379

RESUMO

Resumen Introducción: El cáncer colorrectal se ha convertido en el tercer cáncer a nivel mundial en cuanto a incidencia y cuarto en mortalidad. Al diagnóstico, aproximadamente el 25% de los pacientes tendrán metástasis hepáticas. Con tratamiento adecuado el pronóstico de los pacientes etapa IV alcanza una sobrevida de 40% a 5 años. Con nuestro trabajo queremos evaluar la respuesta del tumor primario de colon desde el punto de vista imagenológico y anatomopatológico en pacientes con cáncer colorrectal con metástasis hepáticas tratados con quimioterapia y que luego fueron a resección del colon. Materiales y Método: Se trata un estudio retrospectivo y descriptivo, de pacientes con cáncer colorrectal con metástasis hepáticas. Los criterios de inclusión fueron que presentaran cáncer de colon o recto superior, con metástasis hepáticas sincrónicas, recibieran al menos 4 ciclos de quimioterapia neoadyuvante y que posteriormente fueran a resección del tumor primario. Resultados: Se reclutaron 9 pacientes, 4 hombres y 5 mujeres. Todos recibieron 4 o más ciclos de quimioterapia previo a la cirugía del tumor primario. De ellos, 8 tuvieron control imagenológico posquimioterapia. Según criterios RECIST, 3 pacientes presentaron respuesta completa, 1 paciente respuesta parcial y 4 enfermedad estable. El estudio anatomopatológico del colon resecado mostró desaparición tumoral macroscópica en 2 pacientes y microscópica en 1 paciente. Conclusiones: La regresión patológica completa en nuestros casos tratados con quimioterapia neoadyuvante es un hecho poco frecuente. Esto nos permite indicar la resección del sitio del tumor colorrectal en todos estos casos.


Introduction: Colorectal cancer has become the third cancer worldwide in terms of incidence and fourth in mortality. At diagnosis approximately 25% of patients will have liver metastases. With adequate treatment, the prognosis of stage IV patients reaches a survival of 40% at 5 years. We want to evaluate the response of the primary tumor of the colon from imaging and anatomopathological point of view in patients with colorectal cancer with liver metastases treated with chemotherapy and who then went to colon resection. Materials and Method: It is a retrospective and descriptive study of patients with stage IV colorectal cancer. The inclusion criteria were that they had cancer of the colon or upper rectum, with synchronous liver metastases, who have received at least 4 cycles of neoadjuvant chemotherapy and that subsequently went to resection of the primary tumor. Results: We recruited 9 patients, 4 men and 5 women. All received 4 or more cycles of chemotherapy prior to primary surgery. Of these, 8 had imaging control after chemotherapy. According to RECIST criteria, 3 patients presented complete response, 1 patient partial response and 4 stable disease. The anatomopathological study of the resected colon showed a macroscopic tumor disappearance in 2 patients, and microscopic in 1 patient. Conclusions: The complete pathological regression in our cases treated with neoadjuvant chemotherapy is a rare occurrence. This allows us to indicate the resection of the colorectal tumor site in all these cases.


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/radioterapia , Neoplasias Hepáticas/secundário , Metástase Neoplásica , Neoplasias Colorretais/mortalidade , Taxa de Sobrevida , Intervalo Livre de Doença , Estadiamento de Neoplasias
9.
Molecules ; 24(3)2019 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-30759785

RESUMO

Colorectal cancer is the third most commonly occurring cancer in men and the second most commonly occurring cancer in women worldwide. We have recently reported that curcuminoid complexes labelled with gallium-68 have demonstrated preferential uptake in HT29 colorectal cancer and K562 lymphoma cell lines compared to normal human lymphocytes. In the present study, we report a new gallium-68-labelled curcumin derivative (68Ga-DOTA-C21) and its initial validation as marker for early detection of colorectal cancer. The precursor and non-radioactive complexes were synthesized and deeply characterized by analytical methods then the curcuminoid was radiolabelled with gallium-68. The in vitro stability, cell uptake, internalization and efflux properties of the probe were studied in HT29 cells, and the in vivo targeting ability and biodistribution were investigated in mice bearing HT29 subcutaneous tumour model. 68Ga-DOTA-C21 exhibits decent stability (57 ± 3% after 120 min of incubation) in physiological media and a curcumin-mediated cellular accumulation in colorectal cancer cell line (121 ± 4 KBq of radiotracer per mg of protein within 60 min of incubation). In HT29 tumour-bearing mice, the tumour uptake of 68Ga-DOTA-C21 is 3.57 ± 0.3% of the injected dose per gram of tissue after 90 min post injection with a tumour to muscle ratio of 2.2 ± 0.2. High amount of activity (12.73 ± 1.9% ID/g) is recorded in blood and significant uptake of the radiotracer occurs in the intestine (13.56 ± 3.3% ID/g), lungs (8.42 ± 0.8% ID/g), liver (5.81 ± 0.5% ID/g) and heart (4.70 ± 0.4% ID/g). Further studies are needed to understand the mechanism of accumulation and clearance; however, 68Ga-DOTA-C21 provides a productive base-structure to develop further radiotracers for imaging of colorectal cancer.


Assuntos
Neoplasias Colorretais/radioterapia , Curcumina/química , Curcumina/farmacologia , Radioisótopos de Gálio/química , Radioisótopos de Gálio/farmacologia , Compostos Heterocíclicos com 1 Anel/química , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/metabolismo , Curcumina/metabolismo , Feminino , Radioisótopos de Gálio/metabolismo , Células HT29 , Compostos Heterocíclicos com 1 Anel/metabolismo , Humanos , Camundongos Nus , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/metabolismo , Compostos Radiofarmacêuticos/farmacologia , Distribuição Tecidual
10.
J Surg Oncol ; 119(4): 532-538, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30609038

RESUMO

BACKGROUND AND OBJECTIVES: To assess the efficacy and the effect of biologic effective dose (BED) on outcomes treated by hypofractionated stereotactic radiotherapy for colorectal cancer (CRC) oligometastases. METHODS: Patients with CRC oligometastases treated at our hospital between 2009 and 2016 were included. The relationship between BED and risk of local recurrence was assessed. Recursive partitioning analysis (RPA) was used to evaluate the effect of BED on outcomes. RESULTS: A total of 48 patients were included in this study. Median follow-up time of surviving patient was 15 months (range, 3-82 months). The 1-year local control rate was 85%. The risk of local recurrence decreased sharply when BED was >90 Gy10 . RPA showed BED of 100 Gy 10 was the appropriate dose for recurrence risk stratification. BED ≥ 100 Gy 10 was significantly better than BED < 100 Gy 10 for achieving 1-year local control (94.4% vs 63.2%; P = 0.022) and 1-year OS (100% vs 73.4%; P = 0.028). One patient who received long-term antiangiogenic treatment died of massive intestinal hemorrhage; no other grade 3 or above early or late events were observed. CONCLUSIONS: Hypofractionated stereotactic radiotherapy provides favorable outcomes with acceptable toxicities in CRC oligometastases. BED ≥ 100 Gy is associated with better outcomes.


Assuntos
Neoplasias Colorretais/radioterapia , Fracionamento da Dose de Radiação , Radiocirurgia/métodos , Adulto , Idoso , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Radiocirurgia/efeitos adversos
11.
Postgrad Med ; 131(2): 163-170, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30633608

RESUMO

OBJECTIVES: To investigate the impact of location of metastases, and therapeutic modality on clinical outcomes in patients with metastatic colorectal cancer (CRC). METHODS: Data for metastatic CRC patients were sourced from the Surveillance, Epidemiology, and End Results (SEER) database (SEER ID: 15309-Nov2017). Patients were classified as follows: Group 1 patients had only liver metastasis; Group 2 patients had liver and lung metastasis; Group 3 patients had more than two metastasis sites. Patients were treated with surgery alone, radiation alone, or surgery plus radiation. The main study outcomes were (1) cancer-specific mortality and (2) survival benefit associated with treatment modality. RESULTS: A total number of 15,510 patients were included in this study. In Groups 1 and 2, patients treated with surgery plus radiation had a higher cumulative survival compared to other treatment groups (p-value <.001). Group 3 patients showed no significant difference in cumulative survival between the different treatment modalities (p-value = .218). Group 1 patients who received surgery plus radiation had a significantly lower risk of mortality compared to the other treatment groups (p-value <.001), and Group 2 patients who either received radiation treatment alone or surgery plus radiation had a significantly lower risk for mortality than patients who received other treatment modalities (p-value <.001). Multivariate analysis adjusting for known prognostic factors such as tumor sidedness and race did not alter the observed risk conferred by metastasis sites and treatment modalities. CONCLUSION: Stratification by metastases sites, and by treatment modality can help multidisciplinary teams to reach a treatment consensus for metastatic CRC.


Assuntos
Neoplasias Colorretais/terapia , Idoso , Neoplasias Colorretais/patologia , Neoplasias Colorretais/radioterapia , Neoplasias Colorretais/cirurgia , Terapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Programa de SEER , Análise de Sobrevida , Resultado do Tratamento
12.
BMJ Case Rep ; 12(1)2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-30674489

RESUMO

Rectal carcinoma with metastasis to skeletal muscle is a rare finding. According to literature review, 17 cases of skeletal muscle metastasis from colorectal carcinoma have been documented where only six cases were rectal carcinomas.We discuss a case of a middle-aged man with a known history of high-grade mucinous adenocarcinoma of the rectum, status post abdominoperineal resection followed by adjuvant radiotherapy and chemotherapy. During the planned chemotherapy course, a right proximal thigh subcutaneous mass was incidentally found which on subsequent biopsy proved to be metastatic from rectal primary site. On subsequent 18F-FDG (Fluorodeoxyglucose) positron emission tomography (PET)/CT scan after completion of chemotherapy for the purpose of treatment response evaluation, only FDG-avid lesion was residual right proximal thigh metastatic mass without involvement of other common sites, such as liver and lung. In this case, the 18F-FDG-PET/CT scan was able to exclude additional metastatic sites and also evaluate the patient's treatment response.


Assuntos
Adenocarcinoma/secundário , Neoplasias Colorretais/secundário , Neoplasias Musculares/diagnóstico por imagem , Neoplasias Musculares/secundário , Coxa da Perna/patologia , Adenocarcinoma/diagnóstico por imagem , Quimiorradioterapia Adjuvante , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/radioterapia , Neoplasias Colorretais/cirurgia , Diagnóstico Diferencial , Fluordesoxiglucose F18 , Humanos , Masculino , Metastasectomia/métodos , Pessoa de Meia-Idade , Neoplasias Musculares/patologia , Neoplasias Musculares/cirurgia , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Metástase Neoplásica , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Doenças Raras , Coxa da Perna/diagnóstico por imagem , Resultado do Tratamento
13.
Rev Med Liege ; 73(7-8): 419-424, 2018 Jul.
Artigo em Francês | MEDLINE | ID: mdl-30113786

RESUMO

Brain metastases occur in 1 to 4 % of patients with colorectal cancer and are unique in 0.5 % of them. Because of their infrequent nature, brain imaging is not recommended in the systematic follow-up of these patients. We report here an exceptional case of a unique brain metastasis in a very unusual position. An 82-year-old patient with a colorectal cancer of the splenic angle that was treated with surgery and adjuvant chemotherapy, developed a series of neurological symptoms over four to six weeks: difficulty swallowing, loss of strength in the four limbs and balance disorders. These symptoms urged the performance of a nuclear magnetic resonance to exclude a central neurological lesion. MRI revealed a nodular tumor of 20 millimeters in the major transverse axis and 17 millimeters in the cerebro-caudal axis, located on the ventral portion of the protuberance. Because of its localization, surgery was not possible and the lesion was treated with Cyberknife radiosurgery. Thanks to the treatment, the lesion decreased in size and the symptoms improved significantly. Despite an initially very poor prognosis in view of the localization of the metastasis, the patient is alive and in excellent general condition more than eight months after the diagnosis of recurrence.


Assuntos
Adenocarcinoma/patologia , Neoplasias Encefálicas/secundário , Neoplasias Colorretais/patologia , Ponte/patologia , Adenocarcinoma/radioterapia , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/radioterapia , Neoplasias Colorretais/radioterapia , Humanos , Masculino , Radiocirurgia , Resultado do Tratamento
14.
Int J Oncol ; 53(4): 1667-1680, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30085332

RESUMO

Irinotecan, an analog of camptothecin, which is an inhibitor of topoisomerase I, is currently used in the treatment of metastatic colorectal cancer. Camptothecin derivatives have been demonstrated to exert radiosensitizing effects on several types of cancer cells. However, to date, at least to the best of our knowledge, few studies have examined these effects in colorectal cancer cell lines. In the present study, we examined the radiosensitizing effects of irinotecan on the p53-mutant colorectal cancer cell lines, HT29 and SW620, and explored the potential underlying mechanisms. Drug cytotoxicity tests revealed that the 24 h half-maximal inhibitory concentrations (IC50s) of irinotecan as a single agent were 39.84 µg/ml (HT29 95% CI, 38.27-41.48) and 96.86 µg/ml (SW620 95% CI, 89.04-105.4); finally, concentrations <2 µg/ml were used in the subsequent experiments. Clonogenic assays revealed that irinotecan exerted radiosensitizing effects on the HT29 and SW620 cells, and the sensitivity enhancement ratios (SERs) at 2 Gy increased with increasing concentrations (SER at 2 Gy, 1.41 for the HT29 cells, 1.87 for the SW620 cells; with irinotecan at 2 µg/ml). Subsequently, the cells were divided into 4 groups: The control group, irinotecan group, radiation group and combination group. Compared with the control, irinotecan and radiation groups, the combination group had the slowest cell growth rate and the most obvious foci of Ser139p­Î³H2AX. Combined treatment resulted in a firstly decreased and then increased M phase arrest and led to the most significant G2/M phase arrest, followed by the most significant increase in apoptosis. The results of western blot analysis indicated that the expression levels of proteins related to the DNA damage response system (Ser1981p­ATM, Ser345p­Chk1, Thr68p­Chk2 and Ser139p­Î³H2AX) and the cell cycle (Tyr15p­Cdc2 and cyclin B1) exhibited the greatest increase in the combined group. In addition, the expression of Ser216p­Cdc25C was also increased in the combined group, indicating that irinotecan likely radiosensitized the p53-mutant HT29 and SW620 cells through the ATM/Chk/Cdc25C/Cdc2 pathway.


Assuntos
Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/radioterapia , Proteína Supressora de Tumor p53/genética , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteína Quinase CDC2/genética , Camptotecina/análogos & derivados , Camptotecina/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos da radiação , Proliferação de Células/efeitos da radiação , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/efeitos da radiação , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HT29 , Humanos , Irinotecano , Proteínas Proto-Oncogênicas pp60(c-src)/genética , Radiossensibilizantes/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fosfatases cdc25/genética
15.
Nucl Med Commun ; 39(10): 915-920, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30124600

RESUMO

PURPOSE: Yttrium-90 (Y)-resin microspheres are prescribed using activity. We evaluated overall survival (OS) and radiographic tumor response after selective internal radiation therapy (SIRT) with resin microspheres in patients with liver metastases from colorectal cancer. PATIENTS AND METHODS: We retrospectively reviewed 60 metastatic colorectal cancer patients treated at our institution with SIRT using Y-resin microspheres. Each patient underwent pre-SIRT MRI or computed tomography imaging of the liver with intravenous contrast. Patients underwent post-treatment imaging at 2-3-month intervals with response assessed according to unidimensional Response Evaluation Criteria in Solid Tumors (RECIST) criteria as well as published three-dimensional volumetric criteria. We then related the prescribed activity established by the body surface area method and the corresponding prescribed dose to radiographic treatment response and OS. RESULTS: The median follow-up after the first SIRT treatment was 8.9 months. The mean prescribed activity and the prescribed dose were 26.6 mCi and 52.8 Gy, respectively. OS was not significantly associated with either prescribed activity or prescribed dose. Prescribed dose was also not related to response. However, a significant relationship was found between a higher prescribed activity and an improved radiographic response by RECIST (P=0.04) at the second follow-up. CONCLUSION: The prescribed activity of Y-resin microspheres may be correlated with radiographic response by RECIST criteria at 4-6 months post-treatment. For a more accurate prediction of response, a valid dose calculation model based on post-Y PET dosimetry is likely needed given the heterogeneous dose delivery seen in SIRT.


Assuntos
Resinas Acrílicas/química , Neoplasias Colorretais/patologia , Neoplasias Colorretais/radioterapia , Microesferas , Doses de Radiação , Radioisótopos de Ítrio/química , Radioisótopos de Ítrio/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia , Feminino , Humanos , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Estudos Retrospectivos , Resultado do Tratamento
16.
Oncol Rep ; 40(3): 1554-1564, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30015983

RESUMO

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and common cause of cancer­related deaths. Radiotherapy has become a routine treatment for CRC. However, radioresistance affects therapeutic efficacy. Long non­coding RNA urothelial carcinoma associated 1 (UCA1) has been demonstrated to be overexpressed in several tumors and predicts a poor prognosis. In the present study, we revealed that lncRNA­UCA1 was overexpressed in colorectal cancer tissue and colon cancer cells when compared to normal tissue and cells. Quantitative real­time PCR revealed that the expression of UCA1 was significantly higher in CRC tissues after chemoradiotherapy. Downregulation of UCA1 enhanced the radiosensitivity of CCL244 cells via inhibition of the colony formation, proliferation and promotion of radiation­induced apoptosis and G2/M arrest. Moreover, downregulation of UCA1 suppressed the epithelial­mesenchymal transition (EMT) in CCL244 cells.


Assuntos
Biomarcadores Tumorais/genética , Movimento Celular , Neoplasias Colorretais/radioterapia , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , RNA Longo não Codificante/genética , Tolerância a Radiação/genética , Idoso , Apoptose , Estudos de Casos e Controles , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Invasividade Neoplásica , Prognóstico , Células Tumorais Cultivadas , Cicatrização , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Int J Nanomedicine ; 13: 3541-3552, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29950834

RESUMO

Background: This study investigated the effectiveness and underpinning mechanisms of radiosensitization using octaarginine (R8)-modified gold nanoparticle-poly(ethylene glycol) (GNP-PEG-R8) in colorectal cancer cell line LS180 to megavoltage radiotherapy in vitro. Method: In-house synthesized GNP-PEG was characterized by transmission electron microscopy, dynamic light scattering, ultraviolet-visible spectrophotometry, and X-ray photoelectron spectroscopy. Inductively coupled plasma mass spectroscopy was used to quantify internalization. Direct cytotoxicity was established using the Cell Counting Kit-8, while radiosensitivity was determined using the gold standard in vitro clonogenic assay. Cell-cycle distribution, apoptosis, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were analyzed by flow cytometry, further exploring the key mechanisms driving GNP-PEG-R8 radiosensitization. Results: The core GNP diameter was 6.3±1.1 nm (mean±SD). Following functionalization, the hydrodynamic diameter increased to 19.7±2.8 nm and 27.8±1.8 nm for GNP-PEG and GNP-PEG-R8, with respective surface plasmon resonance peaks of 515 nm and 525 nm. Furthermore, incorporation of the R8 significantly increased nanoparticle internalization compared to GNP-PEG (p<0.001) over a 1 h treatment period. Functionalized GNPs confer little cytotoxicity below 400 nM. In clonogenic assays, radiation combined with GNP-PEG-R8 induced a significant reduction in colony formation compared with radiation alone, generating a sensitizer enhancement ratio of 1.59. Furthermore, GNP-PEG-R8 plus radiation predominantly induced cell-cycle arrest in the G2/M phase, increasing G2/M stalling by an additional 10% over GNP-PEG, markedly promoting apoptosis (p<0.001). Finally, ROS levels and alterations in MMP were investigated, indicating a highly significant (p<0.001) change in both parameters following the combined treatment of GNP-PEG-R8 and radiation over radiation alone. Conclusion: R8-modified GNPs were efficiently internalized by LS180 cells, exhibiting minimal cytotoxicity. This yielded significant radiosensitization in response to megavoltage radiation. GNP-PEG-R8 may enhance radiosensitivity by arresting cell cycle and inducing apoptosis, with elevated ROS identified as the likely initiator.


Assuntos
Neoplasias Colorretais/radioterapia , Ouro/química , Nanopartículas Metálicas/química , Oligopeptídeos/química , Tolerância a Radiação , Apoptose/efeitos da radiação , Ciclo Celular/efeitos da radiação , Morte Celular/efeitos da radiação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos da radiação , Neoplasias Colorretais/patologia , Endocitose/efeitos da radiação , Humanos , Hidrodinâmica , Potencial da Membrana Mitocondrial/efeitos da radiação , Nanopartículas Metálicas/ultraestrutura , Espécies Reativas de Oxigênio/metabolismo , Espectrofotometria Ultravioleta
18.
J Surg Oncol ; 118(1): 50-60, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29878362

RESUMO

BACKGROUND AND OBJECTIVES: Liver metastases are indicators of advanced disease in patients with colorectal cancer. Liver resection offers the best possibility of long-term survival. Surgical strategies have evolved in complexity in order to offer resection to a greater number of patients, requiring specialized multidisciplinary care. The current paper focused on analyzing outcomes of patients treated after the development of a dedicated cancer center in our institution. METHODS: Patients operated on for CLM from our databank were paired through propensity score matching (PSM), and the initial experience of surgery for CLM was compared with the treatment performed after specialized multidisciplinary management. The demographic, oncological, and surgical features were analyzed between groups. RESULTS: Overall, 355 hepatectomies were performed in 336 patients. Patients operated on during the second era of had greater use of preoperative chemotherapy (P < 0.001) as well as exposure to more effective oxaliplatin-based regimens (P < 0.001). Surgical management also changed, with minor (P = 0.002) and non-anatomic (P = 0.006) resections preferred over major operations. We also noted an increased number of minimally invasive resections (P < 0.001). CONCLUSION: Treatment in a multidisciplinary cancer center led to changes in oncological and surgical management. Perioperative chemotherapy was frequently employed, and surgeons adopted a conservative approach to liver parenchyma.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia Adjuvante , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/radioterapia , Feminino , Hepatectomia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/radioterapia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Assistência Perioperatória/métodos , Pontuação de Propensão
19.
Jpn J Clin Oncol ; 48(6): 548-554, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29722825

RESUMO

Background: There is growing interest in the use of stereotactic ablative radiotherapy (SABR) for oligometastases. However, extreme caution should be exercised in treating tumors closely located to organs at risk (OARs) with SABR. To reduce complications, we have applied split-course SABR to oligometastases closely located to OARs or to those being retreated with radiotherapy. Methods: We retrospectively reviewed the records of patients with oligometastases who were treated with planned split-course SABR between January 2012 and December 2016. Results: A total of 23 patients with 29 oligometastatic lesions were enrolled. The primary diagnoses were bone and soft tissue cancers in 13 lesions, liver cancers in 12 lesions, and colorectal cancers in four lesions. The median tumor volume was 78 cm3 (range, 4-1781 cm3). The lesions were treated with 1-3 fractions in the first stage of SABR (first SABR), and one or two fractions in the second stage of SABR (second SABR). The time interval between the two stages was about 4 weeks. A partial response was noted in 16 lesions (55%) after the first SABR, and practical reductions in the doses to OARs were observed in the second SABR compared with the first SABR. The 1-, 2- and 3-year local control rates were 92%, 65% and 43%, respectively. No Grade 4 or 5 toxicities were observed during or after treatment. Conclusion: Split-course SABR appeared to be feasible for the treatment of oligometastases closely located to OARs.


Assuntos
Metástase Neoplásica/radioterapia , Radiocirurgia , Adulto , Idoso , Neoplasias Colorretais/radioterapia , Neoplasias Colorretais/secundário , Relação Dose-Resposta à Radiação , Estudos de Viabilidade , Feminino , Humanos , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Órgãos em Risco , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Carga Tumoral
20.
Anticancer Res ; 38(5): 3111-3114, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29715148

RESUMO

AIM: To design a tool to predict the probability of new cerebral lesions after stereotactic radiosurgery/radiotherapy for patients with 1-3 brain metastases from colorectal cancer. PATIENTS AND METHODS: In 21 patients, nine factors were evaluated for freedom from new brain metastases, namely age, gender, Karnofsky performance score (KPS), tumor type, number, maximum total diameter of all lesions and sites of cerebral lesions, extra-cranial metastases, and time from cancer diagnosis to irradiation. RESULTS: Freedom from new lesions was positively associated with KPS of 90-100 (p=0.013); maximum total diameter ≤15 mm showed a trend for positive association (p=0.09). Points were assigned as: KPS 70-80=1 point, KPS 90-100=2 points, maximum diameter ≤15 mm=2 points and maximum diameter >15 mm=1 point. Six-month rates of freedom from new lesions were 29%, 45% and 100% for those with total scores of 2, 3 and 4 points, respectively, with corresponding 12-month rates of 0%, 45% and 100% (p=0.027). CONCLUSION: This study identified three risk groups regarding new brain metastases after stereotactic irradiation. Patients with 2 points could benefit from additional whole-brain radiotherapy.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Neoplasias Colorretais/radioterapia , Neoplasias Colorretais/secundário , Avaliação de Estado de Karnofsky , Adulto , Idoso , Neoplasias Encefálicas/patologia , Neoplasias Colorretais/patologia , Irradiação Craniana , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiocirurgia , Estudos Retrospectivos
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