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1.
Anticancer Res ; 40(5): 2833-2840, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366431

RESUMO

BACKGROUND/AIM: The prognostic value of the number of harvested negative lymph nodes (NLNs) in patients with node-negative esophageal carcinoma treated by esophagectomy with or without neoadjuvant chemoradiation is unclear. PATIENTS AND METHODS: A total of 136 patients who underwent oncological esophagectomy with two-field lymphadenectomy from 1995 to 2014 were analyzed regarding the prognostic impact of NLNs. 86 patients received primary surgery (group 1) and 50 patients had preoperative chemoradiation followed by surgery (group 2). RESULTS: The 5-year overall survival (OS) was 61.1%. Median lymph node harvest was significantly higher in group 1 (39 vs. 34 in group 2, p=0.007). In group 1, patients with a higher number of negative lymph nodes (>40) had a better OS [57.6% vs. 78.9%, HR=0.5 (0.3-0.9), p=0.026], whereas there was no significant difference in group 2 using the same cutoff (47.6% vs. 66.7%, p=0.476). CONCLUSION: The number of NLNs is an independent prognostic factor for patients with esophageal carcinoma treated by primary esophagectomy, but not in patients after neoadjuvant chemoradiation.


Assuntos
Quimiorradioterapia Adjuvante/métodos , Esofagectomia/métodos , Linfonodos/patologia , Esofagectomia/mortalidade , Feminino , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
2.
PLoS One ; 15(1): e0227738, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31945122

RESUMO

OBJECTIVES: Incidence of oral cavity squamous cell carcinomas is rising worldwide, and population characterization is important to follow for future trends. The aim of this retrospective study was to present a large cohort of primary oral cavity squamous cell carcinoma from all four health regions of Norway, with descriptive clinicopathological characteristics and five-year survival outcomes. MATERIALS AND METHODS: Patients diagnosed with primary treatment-naïve oral cavity squamous cell carcinomas at all four university hospitals in Norway between 2005-2009 were retrospectively included in this study. Clinicopathological data from the electronic health records were compared to survival data. RESULTS: A total of 535 patients with primary treatment-naïve oral cavity squamous cell carcinomas were identified. The median survival follow-up time was 48 months (range 0-125 months) after treatment. The median five-year overall survival was found to be 47%. Median five-year disease-specific survival was 52%, ranging from 80% for stage I to 33% for stage IV patients. For patients given treatment with curative intent, the overall survival was found to be 56% and disease-specific survival 62%. Median age at diagnosis was 67 years (range 24-101 years), 64 years for men and 72 years for women. The male: female ratio was 1.2. No gender difference was found in neither tumor status (p = 0.180) nor node status (p = 0.266), but both factors influenced significantly on survival (p<0.001 for both). CONCLUSIONS: We present a large cohort of primary treatment-naïve oral cavity squamous cell carcinomas in Norway. Five-year disease-specific survival was 52%, and patients eligible for curative treatment had a five-year disease-specific survival up to 62%.


Assuntos
Metástase Linfática/patologia , Neoplasias Bucais/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia Adjuvante/métodos , Feminino , Seguimentos , Humanos , Metástase Linfática/terapia , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/patologia , Mucosa Bucal/cirurgia , Neoplasias Bucais/patologia , Neoplasias Bucais/terapia , Esvaziamento Cervical , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Noruega/epidemiologia , Prognóstico , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
3.
Int J Radiat Oncol Biol Phys ; 106(3): 556-563, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31707122

RESUMO

PURPOSE: Surgery is standard treatment for rectal cancer, but neoadjuvant chemoradiation therapy (CRT) may result in clinical complete response (cCR) in select patients, allowing for nonsurgical management (NSM). Prospective studies of NSM strategies are sparse, however, and long-term data on quality of life (QoL) are limited. We conducted a single-arm phase 2 trial of high-dose CRT for NSM of distal rectal cancer; we report secondary long-term patient-reported outcomes (PROs), local regrowth, and overall survival in patients managed nonsurgically. METHODS AND MATERIALS: Fifty-one patients with resectable, T2 or T3, N0-N1, low adenocarcinoma received 65 Gy (intensity modulated radiation therapy, brachytherapy boost) and oral tegafur-uracil. Patients with cCR 6 weeks after treatment (clinical examination, magnetic resonance imaging, biopsy) were referred for observation and followed closely with clinical examination, endoscopy, positron emission tomography/computed tomography, and PROs for 5 years. Overall colorectal cancer-specific QoL and specific symptom scores were evaluated at baseline and in follow-up and compared between time points. Local regrowth was estimated using cumulative incidence and overall survival using Kaplan-Meier estimates. RESULTS: Forty patients achieved cCR after treatment; 29 were in follow-up at 24 months, 21 at 36 months, and 20 at 60 months. PRO questionnaire completion rates were 90% at 24 months, 100% at 36 months, and 85% at 60 months for patients still in follow-up. Average QoL score did not differ between baseline (median 11.1) and 24 months (13.7), 48 months (11.1), or 60 months (6.9). Only rectal bleeding deteriorated from baseline, with bowel- and bladder-related symptom scores otherwise unchanged in follow-up. At median follow-up of 5.0 years, local regrowth rate and overall survival were 31% (95% confidence interval, 15%-47%) and 85% (95% confidence interval, 75%-97%), respectively. CONCLUSIONS: Long-term follow-up after NSM of distal rectal cancer showed excellent general colorectal cancer QoL and local symptom scores. Our study results indicate that high-dose CRT followed by organ preservation might be an alternative to standard treatment.


Assuntos
Adenocarcinoma/terapia , Quimiorradioterapia Adjuvante/métodos , Tratamentos com Preservação do Órgão/métodos , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Neoplasias Retais/terapia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Idoso , Braquiterapia/métodos , Intervalos de Confiança , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Dosagem Radioterapêutica , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia
4.
Int J Cancer ; 146(6): 1606-1617, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-31310010

RESUMO

Using a method optimized in hepatocellular carcinoma (HCC), we established patient-derived xenograft (PDX) models with an increased take rate (42.2%) and demonstrated that FBS +10% dimethyl sulfoxide exhibited the highest tumor take rate efficacy. Among 254 HCC patients, 103 stably transplantable xenograft lines that could be serially passaged, cryopreserved and revived were established. These lines maintained the diversity of HCC and the essential features of the original specimens at the histological, transcriptome, proteomic and genomic levels. Tumor engraftment was associated with lack of encapsulation, poor tumor differentiation, large size and overexpression of cancer stem cell biomarkers, and was an independent predictor for overall survival and tumor recurrence after resection. To confirm the preclinical value of the PDX model in HCC treatment, several antitumor agents were tested in 16 selected PDX models. The results revealed a high degree of pharmacologic heterogeneity in the cohort, as well as heterogeneity to different agents in the same individual. The sorafenib responses observed between HCC patients and the corresponding PDXs were also consistent. After molecular characterization of the PDX models, we explored the predictive markers for sorafenib response and found that mitogen-activated protein kinase kinase kinase 1 (MAP3K1) might play an important role in sorafenib resistance and sorafenib response is impaired in patients with MAP3K1 downexpression. Our results indicated that PDX models could accurately reproduce patient tumors biology and could aid in the discovery of new treatments to advance in precision medicine.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Quimiorradioterapia Adjuvante/métodos , Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos , Feminino , Seguimentos , Perfilação da Expressão Gênica , Genômica , Hepatectomia , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , MAP Quinase Quinase Quinase 1/metabolismo , Masculino , Pessoa de Meia-Idade , Estudo de Prova de Conceito , Estudos Prospectivos , Inibidores de Proteínas Quinases/administração & dosagem , Sorafenibe/administração & dosagem , Resultado do Tratamento
5.
Eur Radiol ; 30(1): 224-238, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31350587

RESUMO

OBJECTIVES: To measure the diagnostic performance of a new radiologic pattern on restaging magnetic resonance (MR) high-resolution T2-weighted imaging (T2-WI)-the split scar sign-for the identification of sustained complete response (SCR) after neoadjuvant therapy in rectal cancer. METHODS: Institutional review board approval was obtained for this retrospective study and the informed consent requirement was waived. Fifty-eight consecutive patients with rectal cancer who underwent neoadjuvant therapy were enrolled. Two radiologists blindly and independently reviewed restaging pelvic MR imaging and recorded the presence/absence of the split scar sign (mrSSS). On a second round, they also assessed the relative proportion of intermediate signal intensity on T2-WI (mrT2) and of high signal intensity on high b-value diffusion-weighted imaging (mrDWI). Endoscopic response grading records were retrieved. Qui-square test was employed in search for associations between SCR, defined as pathologic complete response or long-term recurrence-free clinical follow-up, and mrSSS, mrT2, mrDWI and endoscopy. Interobserver agreement for imaging parameters was estimated using Cohen's kappa (k). RESULTS: mrSSS was significantly associated with SCR, with specificity = 0.97/0.97, sensitivity = 0.52/0.64, PPV = 0.93/0.94, NPV = 0.73/0.78, and AuROC = 0.78/0.83, for observers 1/2, respectively. mrDWI was significantly associated with SCR for observer 2, with specificity = 0.76, sensitivity = 0.60, PPV = 0.65, NPV = 0.71, and AuROC = 0.69. mrT2 and endoscopy were not discriminative. Interobserver agreement was substantial for mrSSS (k = 0.69), moderate for mrDWI (k = 0.46), and poor for mrT2 (k = 0.17). CONCLUSION: The split scar sign is a simple morphologic pattern visible on restaging T2-WI which, although not sensitive, is very specific for the identification of sustained complete responders after neoadjuvant therapy in rectal cancer. KEY POINTS: • The split scar sign is a morphologic pattern visible on high-resolution T2-weighted MR imaging in rectal cancer patients after neoadjuvant therapy. It therefore does not require any changes to standard protocol. • At first restaging pelvic MR imaging (mean: 9.1 weeks after the end of radiotherapy), the split scar sign identified patients who sustained a complete response with very high specificity (0.97) and positive predictive value (0.93-0.94). • The split scar sign has the potential to improve patient selection for "watch-and-wait" after neoadjuvant therapy in rectal cancer.


Assuntos
Quimiorradioterapia Adjuvante/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Retais/patologia , Adulto , Idoso , Cicatriz/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia , Neoplasias Retais/diagnóstico , Neoplasias Retais/terapia , Indução de Remissão , Estudos Retrospectivos , Sensibilidade e Especificidade
6.
Rev. cuba. estomatol ; 56(4): e2108, oct.-dez. 2019. graf
Artigo em Espanhol | LILACS | ID: biblio-1093256

RESUMO

RESUMEN Introducción: El carcinoma ameloblástico es una entidad rara que surge como una neoplasia primaria o a partir de un ameloblastoma preexistente. El colgajo de músculo temporal es una opción terapéutica frecuentemente empleada para la reconstrucción del defecto resultante luego de la exéresis quirúrgica. Objetivo: Presentar un caso clínico de restauración estética y funcional mediante reconstrucción con colgajo temporal de un defecto maxilar por exéresis de carcinoma ameloblástico, dada la infrecuente presentación de esta entidad. Caso clínico: Mujer de 49 años de edad, que refiere "una bola" en el paladar de 9 meses de evolución. Al examen físico facial presenta aumento de volumen en región infraorbitaria izquierda. Se realizó una tomografía axial computarizada en la que se constató la presencia de imagen hiperdensa en seno maxilar izquierdo con calcificación en su interior, produciendo lisis del hueso nasal y hueso cigomático infiltrando partes blandas. Se tomó muestra para biopsia que informó tumor de alto grado de malignidad correspondiente a carcinoma ameloblástico. En estudio radiográfico de tórax no se apreció presencia de metástasis pulmonar. Se realizó maxilarectomía de infra y mesoestructura, resección de la lesión con margen oncológico de seguridad y se reconstruyó el defecto palatino con colgajo pediculado del músculo temporal. Se indicó quimio y radioterapia como terapia adyuvante al tratamiento quirúrgico. Se mantuvo el chequeo posoperatorio mostrándose buena evolución clínica y una epitelización secundaria del músculo temporal en el área palatina con restauración de las funciones. Conclusiones: Se presentó un caso clínico de carcinoma ameloblástico, entidad patológica de escasa frecuencia. La cirugía constituyó el pilar de tratamiento utilizado. Una vez realizada la resección quirúrgica se reconstruyó el defecto palatino, utilizándose el colgajo del músculo temporal, opción útil para lograr el restablecimiento de las funciones estéticas y funcionales como la deglución y fonación(AU)


ABSTRACT Introduction: Ameloblastic carcinoma is a rare condition emerging as a primary neoplasm or from a preexisting ameloblastoma. Temporalis muscle flap is a therapeutic option frequently used for reconstruction of the defect resulting from surgical exeresis. Objective: Present a clinical case of esthetic and functional restoration by reconstruction with temporalis muscle flap of a maxillary defect caused by exeresis of an ameloblastic carcinoma. The case is presented because of the infrequent occurrence of this condition. Clinical case: A female 49-year-old patient reports "a lump" in her palate of nine months evolution. Physical examination finds an increase in volume in the left infraorbital region. Computed axial tomography was indicated, which revealed the presence of a hyperdense image in the left maxillary sinus with internal calcification causing lysis of the nasal bone and the zygomatic bone, and infiltrating soft tissue. A sample was taken for biopsy, which reported a tumor with a high degree of malignancy corresponding to ameloblastic carcinoma. Chest radiography did not show the presence of lung metastasis. Infra- and mesostructure maxillectomy was performed, the lesion was removed with a surgical safety margin, and the palatine defect was reconstructed with a pediculated temporalis muscle flap. Chemo- and radiotherapy were indicated as adjuvants to the surgical treatment. Postoperative follow-up found good clinical evolution and secondary epithelization of the temporalis muscle in the palatine area with restoration of functions. Conclusions: A clinical case was presented of ameloblastic carcinoma, a condition with a low frequency of occurrence. Surgery was the basic component of the treatment applied. Once surgical resection was performed, the palatine defect was reconstructed by means of a temporalis muscle flap, a useful option to achieve the restoration of esthetic and biological functions, such as swallowing and speech(AU)


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Retalhos Cirúrgicos/cirurgia , Ameloblastoma/diagnóstico por imagem , Neoplasias Maxilomandibulares/patologia , Reconstrução Mandibular/métodos , Quimiorradioterapia Adjuvante/métodos
7.
Am Surg ; 85(11): 1276-1280, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31775971

RESUMO

The use of neoadjuvant chemoradiation therapy in patients with pancreatic adenocarcinoma is emerging as an acceptable therapy option. The effects of neoadjuvant therapy on 30 days' outcomes in patients with pancreatic cancer are not well defined in the literature. NSQIP (2009-2012) was used. Only patients with a diagnosis of pancreatic cancer and those who underwent a Whipple were included in the analysis. Patient who underwent neoadjuvant chemoradiation therapy were compared with those who did not receive therapy. Main outcome measures were as follows: complications, ≥2 units of blood transfusions, length of stay, readmission rates, return to the operating room, and 30-day mortality. A total of 1445 patients (395: neoadjuvant chemoradiation and 1050: no neoadjuvant therapy) were identified. The mean age was 67 ± 12 years, and 51 per cent of the patients were male. Neoadjuvant chemoradiation therapy was associated with increase in readmission rates (18% vs 12.2%, P 0.02), unanticipated return to the operating room (2.3% vs 1.1%, P 0.03) with no difference in mortality rates. Neoadjuvant chemoradiation therapy is associated with increase in inhospital complications. These differences in outcomes may be explained by the more advance stage of pancreatic cancer in these subsets of patients. Resource utilization and preoperative rehabilitation are of utmost significance to overcome this rise in complications associated with neoadjuvant chemoradiation therapy.


Assuntos
Quimiorradioterapia Adjuvante/efeitos adversos , Terapia Neoadjuvante/efeitos adversos , Neoplasias Pancreáticas/terapia , Pancreaticoduodenectomia , Idoso , Quimiorradioterapia Adjuvante/métodos , Feminino , Humanos , Masculino , Método de Monte Carlo , Duração da Cirurgia , Análise de Regressão , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do Tratamento
8.
World J Gastroenterol ; 25(37): 5655-5666, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31602165

RESUMO

BACKGROUND: The factors affecting the prognosis and role of adjuvant therapy in advanced gallbladder carcinoma (GBC) after curative resection remain unclear. AIM: To provide a survival prediction model to patients with GBC as well as to identify the role of adjuvant therapy. METHODS: Patients with curatively resected advanced gallbladder adenocarcinoma (T3 and T4) were selected from the Surveillance, Epidemiology, and End Results database between 2004 and 2015. A survival prediction model based on Bayesian network (BN) was constructed using the tree-augmented naïve Bayes algorithm, and composite importance measures were applied to rank the influence of factors on survival. The dataset was divided into a training dataset to establish the BN model and a testing dataset to test the model randomly at a ratio of 7:3. The confusion matrix and receiver operating characteristic curve were used to evaluate the model accuracy. RESULTS: A total of 818 patients met the inclusion criteria. The median survival time was 9.0 mo. The accuracy of BN model was 69.67%, and the area under the curve value for the testing dataset was 77.72%. Adjuvant radiation, adjuvant chemotherapy (CTx), T stage, scope of regional lymph node surgery, and radiation sequence were ranked as the top five prognostic factors. A survival prediction table was established based on T stage, N stage, adjuvant radiotherapy (XRT), and CTx. The distribution of the survival time (>9.0 mo) was affected by different treatments with the order of adjuvant chemoradiotherapy (cXRT) > adjuvant radiation > adjuvant chemotherapy > surgery alone. For patients with node-positive disease, the larger benefit predicted by the model is adjuvant chemoradiotherapy. The survival analysis showed that there was a significant difference among the different adjuvant therapy groups (log rank, surgery alone vs CTx, P < 0.001; surgery alone vs XRT, P = 0.014; surgery alone vs cXRT, P < 0.001). CONCLUSION: The BN-based survival prediction model can be used as a decision-making support tool for advanced GBC patients. Adjuvant chemoradiotherapy is expected to improve the survival significantly for patients with node-positive disease.


Assuntos
Adenocarcinoma/terapia , Quimiorradioterapia Adjuvante/métodos , Neoplasias da Vesícula Biliar/terapia , Metástase Linfática/terapia , Modelos Biológicos , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Teorema de Bayes , Quimioterapia Adjuvante/métodos , Colecistectomia , Tomada de Decisão Clínica/métodos , Feminino , Vesícula Biliar/patologia , Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Seleção de Pacientes , Prognóstico , Radioterapia Adjuvante/métodos , Estudos Retrospectivos , Programa de SEER/estatística & dados numéricos , Análise de Sobrevida , Taxa de Sobrevida , Fatores de Tempo , Estados Unidos/epidemiologia , Adulto Jovem
9.
J Neurooncol ; 145(2): 385-390, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31606876

RESUMO

PURPOSE: The aim of this study was to determine whether a higher biological effective dose (BED) would result in improved local control in patients treated with fractionated stereotactic radiotherapy (FSRT) for their resected brain metastases. METHODS: Patients with newly diagnosed brain metastases without previous brain radiotherapy were retrospectively reviewed. Patients underwent surgical resection of at least one brain metastasis and were treated with adjuvant FSRT, delivering 25-36 Gy in 5-6 fractions. Outcomes were computed using Kaplan-Meier survival analysis and univariate analysis. RESULTS: Fifty-four patients with 63 post-operative cavities were included. Median follow-up was 16 months (3-60). Median metastasis size at diagnosis was 2.9 cm (0.6-8.1) and median planning target volume was 19.7 cm3 (6.3-68.1). Two-year local control (LC) was 83%. When stratified by dose, 2 years LC rate was 95.1% in those treated with 30-36 Gy in 5-6 fractions (BED10 of 48-57.6 Gy10) versus 59.1% lesions treated with 25 Gy in 5 fractions (BED10 of 37.5 Gy10) (p < 0.001). LC was not associated with resection cavity size. One year overall survival was 68.7%, and was independent of BED10. Symptomatic radiation necrosis occurred in 7.9% of patients and was not associated with dose. CONCLUSION: In the post-operative setting, high-dose FSRT (BED10 > 37.5 Gy10) were associated with a significantly higher rate of LC compared to lower BED regimens. Overall, 25 Gy in 5 fractions is not an adequate dose to control microscopic disease. If selecting a 5-fraction regimen, 30 Gy in five fractions appears to provide excellent tumor bed control.


Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Quimiorradioterapia Adjuvante/métodos , Radiocirurgia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/patologia , Fracionamento da Dose de Radiação , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
10.
Anticancer Res ; 39(10): 5797-5801, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570484

RESUMO

Grade IV glioblastoma multiforme is a deadly disease, with a median survival of around 14 to 16 months. Maximal resection followed by adjuvant radiochemotherapy has been the mainstay of treatment since many years, although survival is only extended by a few months. In recent years, an increasing number of data from in vitro and in vivo research with cannabinoids, particularly with the non-intoxicating cannabidiol (CBD), point to their potential role as tumour-inhibiting agents. Herein, a total of nine consecutive patients with brain tumours are described as case series; all patients received CBD in a daily dose of 400 mg concomitantly to the standard therapeutic procedure of maximal resection followed by radiochemotherapy. By the time of the submission of this article, all but one patient are still alive with a mean survival time of 22.3 months (range=7-47 months). This is longer than what would have been expected.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/terapia , Canabidiol/uso terapêutico , Glioblastoma/tratamento farmacológico , Glioblastoma/terapia , Adolescente , Adulto , Neoplasias Encefálicas/mortalidade , Quimiorradioterapia Adjuvante/métodos , Pré-Escolar , Terapia Combinada/métodos , Feminino , Glioblastoma/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
11.
Radiat Oncol ; 14(1): 176, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619265

RESUMO

BACKGROUND: To assess the comparative efficacy and safety of elective nodal irradiation (ENI) and involved-field irradiation (IFI) in patients with esophageal cancer (EC) receiving neoadjuvant chemoradiotherapy plus surgery (nCRTS). MATERIAL AND METHODS: PubMed, Embase, Cochrane Library, Web of Science and major meetings were searched for randomized controlled trials (RCTs) that compared at least two of the following treatment regimens: nCRTS, neoadjuvant chemotherapy plus surgery (nCTS), and surgery (S) alone. Overall survival (OS) was the primary outcomes of interest, reported as hazard ratio (HR) and 95% confidence intervals (CIs). A Bayesian network meta-analysis was performed to compare all regimens simultaneously. RESULTS: Twenty-nine RCTs with a total of 5212 patients were included in the meta-analysis. Both nCRTS adopting ENI (nCRTS-ENI) (HR = 0.63, 95% CI: 0.48-0.83) and nCRTS adopting IFI (nCRTS-IFI) (HR = 0.75, 95% CI: 0.66-0.86) significantly improved OS compared to S alone. No significant differences in OS, locoregional recurrence, distant metastases, R0 resection and postoperative mortality were observed between nCRTS-ENI and nCRTS-IFI. In subgroup analyses, nCRTS-IFI showed a significant OS advantage over nCTS (HR = 0.78, 95% CI: 0.63-0.96) and S alone (HR = 0.50, 95% CI: 0.38-0.68) for esophagus squamous cell carcinoma (ESCC), but nCRTS-ENI did not; nCRTS-ENI using three-dimensional radiotherapy (3D-RT) resulted in an improved OS compared to that with 2D-RT (HR = 0.58, 95% CI: 0.34-0.99). Based on treatment ranking in term of OS, nCRTS-IFI (0.90) and nCRTS-ENI (0.96) was ranked the most effective treatment for ESCC and esophagus adenocarcinoma (EAC), respectively. CONCLUSION: Either adopting ENI or IFI, nCRTS is likely to be the optimal treatment for resectable EC, and nCRTS-IFI and nCRTS-ENI seem to be more effective for patients with ESCC and EAC, respectively. Future head to head comparison trials are needed to confirm these findings.


Assuntos
Adenocarcinoma/radioterapia , Quimiorradioterapia Adjuvante/métodos , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago/radioterapia , Irradiação Linfática/métodos , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/radioterapia , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Teorema de Bayes , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/terapia , Humanos , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Metanálise em Rede , Resultado do Tratamento
12.
World J Gastroenterol ; 25(39): 5991-6005, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31660035

RESUMO

BACKGROUND: Mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN) is a rare diagnosis, mainly encountered in the gastro-entero-pancreatic tract. There is limited knowledge of its epidemiology, prognosis and biology, and the best management for affected patients is still to be defined. AIM: To investigate clinical-pathological characteristics, treatment modalities and survival outcomes of a retrospective cohort of patients with a diagnosis of MiNEN. METHODS: Consecutive patients with a histologically proven diagnosis of MiNEN were identified at 5 European centres. Patient data were retrospectively collected from medical records. Pathological samples were reviewed to ascertain compliance with the 2017 World Health Organisation definition of MiNEN. Tumour responses to systemic treatment were assessed according to the Response Evaluation Criteria in Solid Tumours 1.1. Kaplan-Meier analysis was applied to estimate survival outcomes. Associations between clinical-pathological characteristics and survival outcomes were explored using Log-rank test for equality of survivors functions (univariate) and Cox-regression analysis (multivariable). RESULTS: Sixty-nine consecutive patients identified; Median age at diagnosis: 64 years. Males: 63.8%. Localised disease (curable): 53.6%. Commonest sites of origin: colon-rectum (43.5%) and oesophagus/oesophagogastric junction (15.9%). The neuroendocrine component was; predominant in 58.6%, poorly differentiated in 86.3%, and large cell in 81.25%, of cases analysed. Most distant metastases analysed (73.4%) were occupied only by a poorly differentiated neuroendocrine component. Ninety-four percent of patients with localised disease underwent curative surgery; 53% also received perioperative treatment, most often in line with protocols for adenocarcinomas from the same sites of origin. Chemotherapy was offered to most patients (68.1%) with advanced disease, and followed protocols for pure neuroendocrine carcinomas or adenocarcinomas in equal proportion. In localised cases, median recurrence free survival (RFS); 14.0 mo (95%CI: 9.2-24.4), and median overall survival (OS): 28.6 mo (95%CI: 18.3-41.1). On univariate analysis, receipt of perioperative treatment (vs surgery alone) did not improve RFS (P = 0.375), or OS (P = 0.240). In advanced cases, median progression free survival (PFS); 5.6 mo (95%CI: 4.4-7.4), and median OS; 9.0 mo (95%CI: 5.2-13.4). On univariate analysis, receipt of palliative active treatment (vs best supportive care) prolonged PFS and OS (both, P < 0.001). CONCLUSION: MiNEN is most commonly driven by a poorly differentiated neuroendocrine component, and has poor prognosis. Advances in its biological understanding are needed to identify effective treatments and improve patient outcomes.


Assuntos
Diferenciação Celular , Neoplasias Intestinais/epidemiologia , Neoplasias Complexas Mistas/epidemiologia , Tumores Neuroendócrinos/epidemiologia , Neoplasias Pancreáticas/epidemiologia , Neoplasias Gástricas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia Adjuvante/métodos , Quimioterapia Adjuvante/métodos , Intervalo Livre de Doença , Europa (Continente)/epidemiologia , Feminino , Humanos , Neoplasias Intestinais/patologia , Neoplasias Intestinais/terapia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Neoplasias Complexas Mistas/patologia , Neoplasias Complexas Mistas/terapia , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/terapia , Cuidados Paliativos/métodos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia
13.
Expert Rev Anticancer Ther ; 19(11): 939-945, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31661989

RESUMO

Introduction: Today, there is a global consensus that adjuvant treatment is mandatory for stage II and III gastric cancer. What remains controversial, however, is what constitutes the best adjuvant therapy. A comprehensive review including published papers, doi documents, and abstracts from the ASCO annual meeting was undertaken to develop this updated review.Areas covered: Adjuvant treatments for stage II or more advanced and potentially curable gastric and gastroesophageal junction (GEJ) adenocarcinoma are, exclusively, reviewed and discussed.Expert opinion: The role of radiation is not yet established for gastric and GEJ cancers. Postoperative chemoradiotherapy offers no survival advantage over chemotherapy alone for patients who undergo D2 surgery. It is not yet clear if neoadjuvant chemoradiotherapy is better than adjuvant chemotherapy. Individualized treatment plans should be determined for many patients as efficacy depends on tumor histology, and toxicity varies enormously among effective options.


Assuntos
Adenocarcinoma/terapia , Neoplasias Esofágicas/terapia , Neoplasias Gástricas/terapia , Adenocarcinoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ásia , Quimiorradioterapia Adjuvante/métodos , Quimioterapia Adjuvante/métodos , Neoplasias Esofágicas/patologia , Junção Esofagogástrica/patologia , Humanos , Estadiamento de Neoplasias , Neoplasias Gástricas/patologia
14.
Surg Oncol ; 30: 33-39, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31500782

RESUMO

BACKGROUND AND OBJECTIVES: Neoadjuvant chemoradiotherapy (nCRT) induces a pathological complete response (pCR) in 25-85% of oesophago-gastric cancer. As surgery entails morbidity and mortality risks and quality of life (QL) impairment, its avoidance in patients without residual disease is desirable. This study aimed to compare quality of life of patients with a cCR who chose surveillance with those who chose surgery. METHODS: Four groups of patients were studied. Group 1(n = 31) were controls; Group 2 (n = 26) had chemoradiotherapy only; Group 3 (n = 31) had oesophagectomy after nCRT; Group 4 (n = 26) had gastrectomy alone. A 33-point novel questionnaire was administered at two 3 month time points. Participants were also interviewed with a validated questionnaire. RESULTS: Mean(±sd) quality of life scores in cCR patients offered surveillance (28.9 ±â€¯4.5) were superior to patients undergoing oesophagectomy (32.3 ±â€¯58. p=0.042) or gastrectomy (33.19 ±â€¯5.9, p=0.004). This result was replicated in the validated questionnaire (p=0.017). There was a trend towards increased reflux-related respiratory symptoms in the oesophagectomy group (7.3 ±â€¯2.2 vs 6.5 ±â€¯1.9; p=0.396) and towards early dumping (8.2 ±â€¯1.4 vs 7.1 ±â€¯1.; p=0.239) and vagotomy-related symptoms (1.82 ±â€¯0.9 vs 1.4 ±â€¯0.6; p=0.438) in the gastrectomy group. CONCLUSIONS: Avoidance of surgery in cCR patients is rewarded with a superior quality of life to those undergoing surgery.


Assuntos
Adenocarcinoma/terapia , Quimiorradioterapia Adjuvante/métodos , Neoplasias Esofágicas/terapia , Esofagectomia/métodos , Terapia Neoadjuvante/métodos , Qualidade de Vida , Conduta Expectante/métodos , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Terapia Combinada , Neoplasias Esofágicas/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida
15.
Br J Surg ; 106(11): 1530-1541, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31436325

RESUMO

BACKGROUND: Tailored neoadjuvant treatment of locally advanced rectal cancer (LARC) may improve outcomes. The aim of this study was to determine early MRI prognostic parameters with which to stratify neoadjuvant treatment in patients with LARC. METHODS: All patients from a prospective, phase II, multicentre randomized study (GRECCAR4; NCT01333709) were included, and underwent rectal MRI before treatment, 4 weeks after induction chemotherapy and after completion of chemoradiotherapy (CRT). Tumour volumetry, MRI tumour regression grade (mrTRG), T and N categories, circumferential resection margin (CRM) status and extramural vascular invasion identified by MRI (mrEMVI) were evaluated. RESULTS: A total of 133 randomized patients were analysed. Median follow-up was 41·4 (95 per cent c.i. 36·6 to 45·2) months. Thirty-one patients (23·3 per cent) developed tumour recurrence. In univariable analysis, mrEMVI at baseline was the only prognostic factor associated with poorer outcome (P = 0·015). After induction chemotherapy, a larger tumour volume on MRI (P = 0·019), tumour volume regression of 60 per cent or less (P = 0·002), involvement of the CRM (P = 0·037), mrEMVI (P = 0·026) and a poor mrTRG (P = 0·023) were associated with poor outcome. After completion of CRT, the absence of complete response on MRI (P = 0·004), mrEMVI (P = 0·038) and a poor mrTRG (P = 0·005) were associated with shorter disease-free survival. A final multivariable model including all significant variables (baseline, after induction, after CRT) revealed that Eastern Cooperative Oncology Group performance status (P = 0·011), sphincter involvement (P = 0·009), mrEMVI at baseline (P = 0·002) and early tumour volume regression of 60 per cent or less after induction (P = 0·007) were associated with relapse. CONCLUSION: Baseline and early post-treatment MRI parameters are associated with prognosis in LARC. Future preoperative treatment should stratify treatment according to baseline mrEMVI status and early tumour volume regression.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Retais/mortalidade , Adolescente , Adulto , Idoso , Quimiorradioterapia Adjuvante/métodos , Intervalo Livre de Doença , Esquema de Medicação , Fluoruracila/administração & dosagem , Humanos , Infusões Intravenosas , Irinotecano/administração & dosagem , Laparoscopia/estatística & dados numéricos , Leucovorina/administração & dosagem , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Oxaliplatina/administração & dosagem , Medicina de Precisão/métodos , Estudos Prospectivos , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Procedimentos Cirúrgicos Robóticos/estatística & dados numéricos , Carga Tumoral , Adulto Jovem
16.
Radiat Oncol ; 14(1): 147, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31426827

RESUMO

BACKGROUND: There is continued debate regarding the optimal combinations of radiation therapy and chemotherapy in the preoperative treatment of locally advanced rectal adenocarcinomas. We report our single-institution experience of feasibility and early oncologic outcomes of short-course preoperative radiation therapy (5 Gy X 5 fractions) followed by consolidation neoadjuvant chemotherapy. METHODS: We reviewed the records of 26 patients with locally advanced rectal adenocarcinoma. All patients underwent short course radiotherapy (5 Gy X 5 fractions) followed by chemotherapy [either modified infusional and bolus 5-fluorouracail and oxalipatin (mFOLFOX6) or capecitabine and oxaliplatin] prior to consideration for surgery. A full course of chemotherapy was defined as at least 8 weeks of chemotherapy. RESULTS: There were five clinical (c) T2, 16 cT3, and five cT4 rectal tumors, with 88% cN+. Twenty-five patients received a median of 4 cycles (range 3 to 8) of mFOLFOX6 (with one cycle defined as a two-week period); one patient received 3 cycles of capecitabine and oxaliplatin. All patients completed SCRT; 81% completed the full course of neoadjuvant chemotherapy with 19% requiring dose reductions in chemotherapy, most commonly due to neuropathy. Nineteen patients underwent post-treatment endoscopic evaluation, and nine patients were noted to achieve a complete clinical response (CCR). Six of the nine patients who achieved CCR opted for a non-operative approach of watch-and-wait. Twenty patients underwent surgical resection; pathologic complete response was observed in seven (35%) of these twenty. The main radiation-associated toxicity was proctitis with CTCAE Grade 2 proctitis observed in seven patients (27%). Post-operative Clavien-Dindo Grade 3 complications within 30 days of surgery were identified in six patients (30%), with no Grade 4 or 5 adverse events. Median length of hospital stay was 4.5 days (range 2-16 days); three patients were readmitted within a 30 day period. CONCLUSIONS: Short course preoperative radiotherapy followed by neoadjuvant chemotherapy was well-tolerated and achieved oncologic outcomes that compare favorably with short-course radiation therapy alone or long-course chemoradiotherapy. This regimen is associated with high rates of clinical and pathologic complete response.


Assuntos
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia Adjuvante/métodos , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/terapia , Neoplasias Retais/terapia , Adenocarcinoma/patologia , Adulto , Idoso , Capecitabina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Oxaliplatina/administração & dosagem , Neoplasias Retais/patologia , Estudos Retrospectivos , Resultado do Tratamento
17.
Eur J Radiol ; 118: 1-9, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31439226

RESUMO

PURPOSE: To develop and validate an Artificial Intelligence (AI) model based on texture analysis of high-resolution T2 weighted MR images able 1) to predict pathologic Complete Response (CR) and 2) to identify non-responders (NR) among patients with locally-advanced rectal cancer (LARC) after receiving neoadjuvant chemoradiotherapy (CRT). METHOD: Fifty-five consecutive patients with LARC were retrospectively enrolled in this study. Patients underwent 3 T Magnetic Resonance Imaging (MRI) acquiring T2-weighted images before, during and after CRT. All patients underwent complete surgical resection and histopathology was the gold standard. Textural features were automatically extracted using an open-source software. A sub-set of statistically significant textural features was selected and two AI models were built by training a Random Forest (RF) classifier on 28 patients (training cohort). Model performances were estimated on 27 patients (validation cohort) using a ROC curve and a decision curve analysis. RESULTS: Sixteen of 55 patients achieved CR. The AI model for CR classification showed good discrimination power with mean area under the receiver operating curve (AUC) of 0.86 (95% CI: 0.70, 0.94) in the validation cohort. The discriminatory power for the NR classification showed a mean AUC of 0.83 (95% CI: 0.71,0.92). Decision curve analysis confirmed higher net patient benefit when using AI models compared to standard-of-care. CONCLUSIONS: AI models based on textural features of MR images of patients with LARC may help to identify patients who will show CR at the end of treatment and those who will not respond to therapy (NR) at an early stage of the treatment.


Assuntos
Inteligência Artificial , Quimiorradioterapia Adjuvante/métodos , Imagem por Ressonância Magnética/métodos , Terapia Neoadjuvante/métodos , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/terapia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Neoplasias Retais/patologia , Reto/diagnóstico por imagem , Reto/patologia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Resultado do Tratamento
18.
Cancer Radiother ; 23(6-7): 716-719, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31421997

RESUMO

Management of resectable esophageal carcinoma is based on a multimodal treatment associating neo-adjuvant chemoradiation before surgery. This therapeutic sequence allows a disease-free survival rate at 2 years around 45% but remains associated with a high post-operative morbidity. In case of definitive chemoradiotherapy, the dose delivered to the macroscopic disease is a controversial topic since decades and the prognosis of patients treated in this setting at the dose of 50Gy remains poor. This article proposes a review of the main published data and the ongoing studies related to the management of these patients.


Assuntos
Carcinoma/terapia , Quimiorradioterapia Adjuvante/métodos , Neoplasias Esofágicas/terapia , Terapia Neoadjuvante , Humanos , Cuidados Pré-Operatórios/métodos , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos
19.
Asian Pac J Cancer Prev ; 20(7): 2003-2008, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31350957

RESUMO

Background: Precise staging of esophageal cancer (EC) is important for selection of optimal treatment option and prognostication. Aim of this study was to assess the role of 18FDG PET/CT in staging and response evaluation to neoadjuvant chemoradiation (nCR) in EC patients using standardized imaging protocol. Material and methods: This prospective study was conducted at PET/CT Section of Department of Radiology, Aga Khan University Hospital Karachi, Pakistan from July 2017 till February 2018. We included 34 biopsy proven EC patients who had 18FDG PET/CT and CT of neck, chest and abdomen as part of initial staging. Eleven patients had post-nCR 18FDG PET/CT using standardized imaging protocol as per EANM guidelines. CT and PET/CT based staging was compared. Based on PERCIST criteria, response evaluation was assessed using change in highest SUVmax (%ΔSUVmax) in baseline and follow-up scans (primary lesion, node or extra-nodal metastases). Results: Mean age of cohort was 57 ± 14 years (23 males and 11 females) having adenocarcinoma (AC) in 23 and squamous cell cancer (SCC) in 11 patients. Mean 18FDG dose, uptake time and hepatic SUVmean for baseline scans were 169 ±54 MBq, 65 ±10 minute and 1.91 ± 0.49 which were within ± 10%, ± 15% and ± 20% for follow-up scans in 11 patients respectively. Mean size (craniocaudal dimension in mm) and SUVmax of primary tumor was 56 ±27 mm and 13.4 ± 4.7. Based on 18FDG PET/CT findings, patients were categorized into N0 (10/34), N1 (09/34), N2 (11/34) and N3 (04/34) while 11/32 had stage IV disease. No significant difference was seen in AC and SCC groups. CT found stage IV disease in 3/34 (09%) while PET/CT found in 11/34 (32%; p value: 0.019) cases. PET/CT showed concordance with CT in 41% while discordance (all with upstaging) seen in 59%. On follow-up PET/CT, complete metabolic response was seen in 5/11 (45%) and partial metabolic response was noted in 6/11 (55% - p value non-significant) patients. Median %ΔSUVmax over primary lesions was 49.84% (-32.69 -100%) while over nodal sites it was 41.18% (-82.60 -100%). Conclusion: We conclude that 18FDG PET/CT was found a sensitive tool in initial staging of EC. Compared with CT, it had higher diagnostic accuracy for distant nodal and extra-nodal metastasis. %ΔSUVmax between baseline and post-nCR studies acquired with standardized protocol had changed management in more than half of our patients. For response evaluation in EC more studies with standardized 18FDG PET/CT imaging protocols are warranted.


Assuntos
Adenocarcinoma/patologia , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia Adjuvante/métodos , Neoplasias Esofágicas/patologia , Fluordesoxiglucose F18 , Terapia Neoadjuvante/métodos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia Adjuvante/normas , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/terapia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/normas , Estadiamento de Neoplasias , Estudos Prospectivos , Compostos Radiofarmacêuticos
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