Expert consensus on PD-L1 expression testing in esophageal carcinoma in China / 中华肿瘤杂志

In recent years, immunotherapy represented by immune checkpoint inhibitors programmed death 1 (PD-1) has made great progress in the treatment of esophageal cancer and is rewriting the global paradigm for the treatment of esophageal cancer. According to current data, only a small number of patients with esophageal cancer could benefit from immunotherapy. Therefore, it is a challenge to screen the potential beneficiaries of PD-1 inhibitors. Studies have shown that the expression level of programmed death-ligand 1 (PD-L1) in esophageal cancer is closely associated with the efficacy of PD-1 inhibitors, and PD-L1 is the most important predictive biomarker of the efficacy of PD-1 inhibitors. With the clinical application of different PD-1 inhibitors and PD-L1 protein expression detection platforms, clarifying the clinical significance and timing of detection of PD-L1 protein expression in esophageal cancer, and establishing a standardized PD-L1 testing procedure, are of great significance to improve the accuracy of detection and reduce the difference between laboratories, so as to maximize the therapeutic benefits for patients. This consensus was finally reached, based on the combination of literature, expert experience, and internal discussion and voting of committee members, to provide an accurate and reliable evidence for clinicians to make decisions.

Repurposed benzydamine targeting CDK2 suppresses the growth of esophageal squamous cell carcinoma / 医学前沿

Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.

Resultados con la utilización de prótesis en el cáncer de esófago y cardias

Introducción: El cáncer de esófago y cardias es una enfermedad grave, en el que más de tres cuartos de los enfermos que se tratan están en fase avanzada. En Cuba existe experiencia con las prótesis esofágicas originales o construidas en el país. Objetivo: Evaluar los resultados de la experiencia de los hospitales universitarios "Comandante Manuel Fajardo" y "Miguel Enríquez" con las prótesis transtumorales en el cáncer de esófago no resecable. Métodos: Se realizó un estudio observacional, descriptivo, retrospectivo, tipo serie de casos, con una muestra de 197 enfermos con cáncer avanzado del esófago en los Hospitales Universitarios "Comandante Manuel Fajardo" y "Miguel Enríquez" tratados con prótesis por presentar un cáncer avanzado del esófago en el período 1995-2020. Resultados: Predominó el sexo masculino, las edades más afectadas fueron la sexta y séptima década. La localización más frecuente del tumor fue en tercio inferior del esófago y cardias y el tipo histológico el carcinoma epidermoide. En el 71 por ciento se utilizaron prótesis rígidas de tubos endotraqueales; en el 20,8 por ciento prótesis de Heering y en el 8,2 por ciento prótesis autoexpansible. En el Hospital Manuel Fajardo la prótesis que más se utilizó fue la rígida de construcción artesanal y en el Hospital Miguel Enríquez la de Heering. La menos utilizada fue la autoexpansible. Se presentó un 10,1 por ciento de complicaciones, sin mortalidad quirúrgica. Conclusiones: Aunque las prótesis autoexpansible son de fácil colocación por endoscopia, es un método ideal pero costoso. La prótesis plástica rígida industrial o artesanal también puede ofrecer calidad de vida sin disfagia, evitan que el enfermo fallezca con una ostomía abdominal(AU)

Introduction: Esophageal and cardia cancer is a serious disease, in which more than three quarters of the treated patients are in advanced stage. In Cuba there is experience with original esophageal prostheses or others domestically built. Objective: To evaluate the results of the experience of the Comandante Manuel Fajardo and Miguel Enriquez university hospitals with transtumoral prostheses in unresectable esophageal cancer. Methods: An observational, descriptive, retrospective, case-series type study was carried out with a sample of 197 patients treated with prosthesis for advanced esophageal cancer in the university hospitals Comandante Manuel Fajardo and Miguel Enríquez in the period 1995-2020. Results: The male sex predominated, while the most affected ages were the sixth and seventh decades. The most frequent tumor location was the lower third of the esophagus and cardia, while squamous cell carcinoma was the most frequent histological type. Rigid prostheses of endotracheal tubes were used in 71 percent; Heering prostheses, in 20.8 percent; and self-expanding prostheses, in 8.2 percent. The most commonly used prostheses at Manuel Fajardo and Miguel Enriquez hospitals were the rigid prosthesis of handmade construction and the Heering prosthesis, respectively. The least used was the self-expanding prosthesis. There was a 10.1 percent of complications, with no surgical mortality. Conclusions: Although self-expanding prostheses are easy to place by endoscopy, it is an expensive method, even being ideal. The industrial or handmade rigid plastic prosthesis can also offer quality of life without dysphagia, avoiding the patient's death with an abdominal ostomy(AU)

Human esophageal fibroblast-derived exosomal miR-21 reduced the cisplatin sensitivity to esophageal carcinoma EC9706 cells

The objective of this study was to investigate the effect of human esophageal fibroblast-derived exosomal miR-21 on cisplatin sensitivity against esophageal squamous EC9706 cells. EC9706 cells were co-cultured indirectly with human esophageal fibroblasts (HEF) or miR-21 mimics transfected-HEF in the transwell system. The exosomes in HEF-culture conditioned medium were extracted by differential ultracentrifugation. EC9706 cells were co-cultured with HEF-derived exosomes directly. The cisplatin sensitivity against EC9706 cells was revealed via half maximal inhibitory concentration (IC50) values using MTT assay. The expressions of miR-21, programmed cell death 4 (PDCD4) mRNA, and gene of phosphate and tension homology deleted on chromosome ten (PTEN) mRNA were determined by qRT-PCR. The changes of the protein level were detected using western blot assay. IC50 values of cisplatin against EC9706 cells were increased after EC9706 cells were co-cultured with either HEF or exosomes derived from miR-21 mimics-transfected HEF. Following the increased level of miR-21, the mRNA expression and protein levels of PTEN and PDCD4 were decreased in EC9706 cells. The cisplatin sensitivity to EC9706 cells was reduced by HEF-derived exosomal miR-21 through targeting PTEN and PDCD4. This study suggested that non-tumor cells in the tumor micro-environment increased the tumor anti-chemotherapy effects through their exosomes.

Nimotuzumab combinado con quimioradioterapia en pacientes con carcinoma epidermoide esofágico avanzado en el mundo real / Nimotuzumab combined with chemoradiotherapy in patients with advanced esophageal squamous cell carcinoma in the real world

Introducción: La supervivencia global de pacientes con cáncer de esófago continúa siendo baja a pesar de los avances terapéuticos realizados en las últimas décadas. Objetivo: Evaluar respuesta al tratamiento y supervivencia global. Métodos: Se realizó un estudio retrospectivo y observacional en pacientes con carcinoma epidermoide esofágico avanzado, tratados con nimotuzumab combinado con quimioradioterapia, atendidos en el Servicio de Oncología Clínica del Hospital Ameijeiras, entre enero 2013 y junio de 2019 (n = 94). Se utilizó chi-cuadrado para la asociación de variables, con un valor p< 0,05. Se evaluó supervivencia global por el método de Kaplan Meier, y la prueba de Log-Rank para la comparación de las curvas. Resultados: La tasa de respuesta objetiva y de control de enfermedad fue 64,9 por ciento y 83 por ciento, respectivamente. El esquema de quimioterapia con cisplatino/fluouracilo fue el empleado con más frecuencia. Las variables con mayor respuesta y significación estadística fueron: ECOG cero, color de piel no blanca, tratamiento radiante ≥ 50 Gy, y más de catorce dosis de nimotuzumab. La mediana de supervivencia fue 13,03 meses (IC95 por ciento -10,9; 15,2), y las variables asociadas a una mayor probabilidad de supervivencia fueron: ECOG cero, dosis de quimioterapia > 75 por ciento de lo planificado, tratamiento radiante ≥ 50 Gy, más de catorce dosis de nimotuzumab, y alcanzar una respuesta objetiva (p< 0,05). Solo 5,8 por ciento de los pacientes presentaron toxicidades clasificadas como grado 3-5. Conclusiones: En condiciones de práctica clínica, este esquema de combinación obtuvo óptimas tasas de respuesta objetiva y supervivencia con buen perfil de toxicidad(AU)

Introduction: Overall survival of esophageal cancer patients remains low despite the therapeutic advances achieved in the last decades. Objective: Evaluate response to treatment and overall survival. Methods: An observational retrospective study was conducted of patients with advanced esophageal squamous cell carcinoma treated with nimotuzumab combined with chemoradiotherapy at the Clinical Oncology Service of Ameijeiras Hospital from January 2013 to June 2019 (n = 94). Association of variables was analyzed with the chi-square test, using a value of p < 0.05. Overall survival was evaluated with the Kaplan-Meier method, whereas the Log-Rank test was used to compare the curves. Results: Objective response and disease control rates were 64.9 percent and 83 percent, respectively. The chemotherapy scheme with cisplatin / fluorouracil was the most commonly applied. The variables with the greatest response and statistical significance were ECOG zero, skin color not white, radiation therapy ≥ 50 Gy and more than 14 doses of nimotuzumab. Median survival was 13.03 months (CI 95 percent -10,9; 15,2), whereas the variables associated to a greater probability of survival were ECOG zero, chemotherapy dose > 75% of plan, radiation therapy ≥ 50 Gy, more than 14 doses of nimotuzumab, and achieving an objective response (p< 0.05). Only 5.8 percent of the patients presented toxicities classified as grades 3-5. Conclusions: In clinical practice conditions, this combination scheme achieved optimum objective response and survival rates with a good toxicity profile(AU)

Caracterización clínico-patológica del cáncer esofágico avanzado en el Hospital Universitario Comandante Faustino Pérez. Matanzas / Clinic-pathologic characterization of the advanced esophagus cancer in the University Hospital Comandante Faustino Perez, Matanzas

RESUMEN Introducción: el cáncer de esófago en estadio avanzado, es uno de los más agresivos. En Cuba ocupa el décimo lugar entre las causas de muerte. Objetivo: caracterizar clínico y patológicamente a los pacientes con cáncer esofágico diagnosticados en el hospital estudiado. Materiales y métodos: se realizó un estudio prospectivo-descriptivo donde se efectuó una caracterización clínico-patológica a 59 pacientes con el diagnóstico endoscópico e histológico de cáncer de esófago, en el Hospital Faustino Pérez Hernández de Matanzas, de enero del 2016 a diciembre del 2017. Se estudiaron variables como: grupo etáreo, sexo, antecedentes patológicos personales y familiares, factores de riesgo, síntomas y signos predominantes en el diagnóstico, tiempo de aparición de los síntomas, tipo endoscópico, localización, tipo histológico, grado de diferenciación histológica, estadio de la enfermedad, tipo de tratamiento y tiempo de vida posterior al diagnóstico. Resultados: predominó el sexo masculino (88.1%) en pacientes mayores de 60 años (52.6%). La disfagia, la astenia y la anorexia fueron los síntomas más frecuentes; el etilismo crónico y el hábito de fumar fueron los factores de riesgo predominantes. La localización anatómica más frecuente fue el tercio medio (54.2%), el tipo endoscópico vegetante (88.1%) y el tipo histológico carcinoma epidermoide bien diferenciado (55.9%). Hubo relación entre el tiempo de inicio de los síntomas entre 3 y 6 meses antes del diagnóstico y el estadio IV de la enfermedad que predominó en 29 pacientes (49.2%). La mayoría de los pacientes recibieron tratamiento oncológico combinado con cirugía paliativa (47.5%) o ningún tratamiento (45.8%) pues el 50.8% de los pacientes fallecieron al mes del diagnóstico demostrando que el diagnóstico del cáncer esofágico se realiza casi siempre en estadios avanzados de la enfermedad cuando son posible pocas opciones terapéuticas. Conclusiones: el cáncer de esófago aún sigue diagnosticándose de forma tardía en estadios avanzados, con elevada prevalencia del carcinoma epidermoide sobre el adedocarcinoma que indica pocas acciones de salud preventivas sobre los factores de riesgo en la población estudiada, existiendo relación entre el estadio avanzado de la enfermedad y el poco tiempo de vida de estos pacientes posterior al diagnóstico.

ABSTRACT Introduction: the advanced-stage esophagus cancer is one of the most aggressive cancers. In Cuba, it is in the tenth place among the death reasons. Objective: to clinically and pathologically characterize the patients with esophageal cancer diagnosed in the mentioned hospital. Materials and methods: a prospective-descriptive study was carried out based on the clinical-histological characterization of 59 patients with the endoscopic and histological diagnosis of esophageal cancer in the Hospital "Faustino Pérez Hernández", of Matanzas, in the period from January 2016 to December 2017. The studied variables were: age group, sex, personal and familiar pathological antecedents, risk factors, symptoms and signs that were predominant in the diagnosis, time passed since the symptoms appeared, endoscopic kind, location, histological kind, level of histological differentiation, disease stage, kind of treatment, and life time after the diagnosis. Results: male sex predominated (88.1 %) in patients older than 60 years (52.6 %). Dysphagia, asthenia and anorexia were the most frequent signs. Alcoholism and smoking were the predominant risk factors. The most frequent anatomic location was the middle third (54.3 %); the endoscopic vegetating kind (88.1 %) and the histological kind well-differentiated epidermoid carcinoma (55.9 %) prevailed. The authors found a relation between the beginnings of the symptoms 3 to 6 months before the diagnosis and the disease IV stage predominating in 29 patients (49.2 %). Most of patients underwent oncologic treatment combined with palliative surgery (47.5 %) or no treatment (45.8 %), because 50.8 % of the patients died a month after the diagnosis, showing that the diagnosis of esophageal cancer is almost always achieved at advanced stages of the disease, when few therapeutic options are possible. Conclusions: esophageal cancer is still being diagnosed late, in advanced stages, with a higher prevalence of the epidermoid carcinoma over the adenocarcinoma. It indicates few health preventive actions on the risk factors among the studied population. There is a relation between the disease advanced stage and the few time patients live after the diagnosis.

Evaluación del efecto antitumoral del nimotuzumab combinado con radioquimioterapia en tumores de esófago / Evaluation of the antitumor effect of nimotuzumab combined with radiochemotherapy in treatment of esophageal tumors

Introducción: el cáncer de esófago en Cuba es una de las cinco primeras causas de muerte por tumores. El tratamiento incluye quimioterapia, radioterapia y cirugía, así como el descubrimiento de nuevos blancos potenciales para la inmunoterapia, entre los que se encuentra el receptor del Factor de Crecimiento Epidérmico. El anticuerpo monoclonal cubano AcM HR3 (nimotuzumab) se estudia actualmente a nivel mundial. Objetivo: evaluar la eficacia y seguridad del nimotuzumab combinado con radioquimioterapia en tumores de esófago inoperable en comparación con el tratamiento habitual en los pacientes atendidos por esta enfermedad en el Hospital Hermanos Ameijeiras, durante los meses de diciembre de 2005 a junio 2010. Método: se diseñó un estudio clínico controlado, aleatorizado, abierto con dos grupos de tratamiento, uno con Radioquimioterapia más Bioterapia y otro con Radioquimioterapia. La variable principal fue la respuesta clínica, con que clasifica la reducción del tumor, de acuerdo al criterio RECIST, en: remisión completa, remisión parcial, estabilización de la enfermedad y progresión. La toxicidad evaluó los eventos adversos que presentaron los pacientes en cada uno de los grupos de tratamiento. Resultados: en relación a la respuesta objetiva se obtuvo una mayor proporción en el grupo de nimotuzumab (88,9 por ciento) contra el grupo control (22,2 por ciento), con una diferencia estadísticamente significativa entre ambos grupos de 66,7 por ciento. Fueron frecuentes los eventos tos, insomnio, síntomas gastrointestinales y dolor retroesternal en el grupo tratado, mientras que en el grupo control las molestias gastrointestinales y la astenia fueron las de mayor aparición. Conclusiones: los pacientes tratados con nimotuzumab presentaron un mejor índice de respuesta objetiva y de control de la enfermedad y su administración fue segura al combinarse con la terapia establecida para el tratamiento del cáncer de esófago inoperable según las normas terapéuticas cubanas(AU)

Introduction: esophageal cancer in Cuba is one of the first five causes of death from tumors. The treatment includes chemotherapy, radiotherapy and surgery as well as the discovery of new potential targets for immunotherapy such as the epidermal growth factor receptor. The Cuban monoclonal antibody AcM HR3 (nimotuzumab) is studied at present internationally. Objective: to evaluate the efficacy and safety of nimotuzumab combined with radiochemotherapy in inoperable esophageal tumors and to compare it with the ordinary treatment given to patients seen at Hermanos Ameijeiras hospital from December 2005 to June 2010. Method: open, controlled, randomized clinical study was designed for two groups of patients, one with radiochemotherapy plus biotherapy and the other one with radiochemotherapy. The main variable was the clinical response with which the tumor reduction is classified in accordance with the RECIST criteria: complete remission, partial remission, disease stabilization and progression. Toxicity tests evaluated the adverse events that occurred in patients of each of the groups. Results: regarding the objective response, a higher proportion was reached in the group with nimotuzumab (88,9 percent) against the control group (22,2 percent), with statistically significant difference between both groups of patients equal to 66,7 percent. Cough, insomnia, gastrointestinal problems and retrosternal pain were frequent in the treatment group whereas the control group suffered gastrointestinal disturbances and asthenia more frequently. Conclusions: the patients treated with nimotuzumab presented better index of objective response and of disease control and its administration was safe when combined with the set therapy for treatment of inoperable esophageal cancer in line with the Cuban therapeutic standards(AU)

A comparison of results by sequential and concurrent chemo radiotherapy in locally advanced carcinoma esophagus.

Aim: Many Trials using sequential and concurrent chemo radiotherapy have been done so far and has established the role of concurrent chemo radiotherapy in treatment of inoperable carcinoma esophagus. In this study, we have compared the results of concurrent chemo radiotherapy with sequential chemo radiotherapy. We have treated inoperable carcinoma esophagus in both the settings and present here the comparison of results in the two settings. Materials and Methods: There were 26 patients of carcinoma esophagus in sequential and 31 in concurrent chemo radiotherapy arm. In sequential arm methotrexate and Cisplatin followed by radiotherapy was given whereas in concurrent arm, Cisplatin was given once weekly along with radiotherapy. Results: The 2 year survival was 38% in sequential and35.5% in the concurrent setting and the median survival was 19.5 and 18 months respectively in the two arms.The toxicities in both the arms were comparable. P value of 0.4774 with confidence interval of 95% was obtained, which is not significant. Dysphagia was improved earlier in sequential than in the concurrent arm. Conclusion: As the results and toxicities in both the arms are almost similar with better symptom control, so larger randomized trials are required to assess the response and the use of methotrexate in sequential chemo radiotherapy can be further explored.

Metronomic weekly paclitaxel in advanced unresectable esophageal cancer.

CONTEXT: Advanced esophageal cancer is aggressive with an expected median survival of 6‑7 months. Combination chemotherapy regimens provide effective palliation, but result in substantial toxicity. MATERIALS AND METHODS: Retrospective analysis of prospectively collected data of patients with advanced esophageal cancer, not amenable to definitive intent therapy who were treated with intravenous weekly paclitaxel. RESULTS: Between October 2010 and August 2011, 51 patients were included. Median age was 56 years, with a male: female ratio of 2.9:1. 29% were mid esophageal and 55% were lower third and gastroesophageal junction tumors. 65% of the tumors had squamous histology. Performance status was > 2 in 45%. 61% patients had received prior therapy, either definitive or palliative. 51% patients were platinum‑pre‑treated and 29% had received prior 3 weekly paclitaxel. 76% patients had distant metastases. Median number of cycles of weekly paclitaxel delivered was 11. 71% of patients had improvement in dysphagia, with a median time to symptom improvement of 9 days. In 72% patients, the feeding nasogastric tube could be removed. Overall response rate was 49% (complete remission: 4%, partial remission: 45%, stable disease: 13%). Median progression free survival was 4.7 months (confidence interval [95% CI: 3.7‑5.7 months]) and median overall survival was 7.5 months (95% CI: 3.1‑11.8 months). Histopathology, performance status and pre‑treatment albumin significantly affected survival. The most common grade 3/4 toxicities included hyponatremia (14%), fatigue (16%), diarrhea (12%), anemia (31%), neutropenia (10%) and febrile neutropenia (4%). CONCLUSIONS: Metronomic weekly paclitaxel chemotherapy may provide palliative benefit in advanced unresectable metastatic esophageal cancer with minimal toxicity.

Revisión bibliográfica de cáncer de esófago / Literature review of esophageal cancer

El cáncer de esófago es una patología asociada a gran mortalidad ya que generalmente su diagnóstico es tardío. Existen múltiples factores de riesgo que pueden influir es su aparición que varían según el tipo histológico presente. El 95 por ciento de estas neoplasias pertenecen a 2 tipos histológicos: Adenocarcinoma y Carcinoma Epidermoide. Gracias a las características anatómicas del esófago, los síntomas pueden aparecer de manera tardía lo que dificulta su sospecha. Existen múltiples estudios por imágenes que permiten hacer un diagnóstico y clasificación de la lesión de manera certera. La cirugía es el procedimiento que presenta mejores resultados curativos, sin embargo no todos los pacientes son candidatos para la misma. Por lo tanto la quimioterapia así como la radioterapia brindan un buen soporte como tratamiento neoadyudante o adyudante.

Tratamiento endoscópico del carcinoma escamoso precoz de esófago por la disección endoscópica de submucosa / Endoscopic treatment of early esophageal squamous carcinoma by the endoscopic submucosal disection

Las nuevas tecnologías de imagen con endoscopios de alta resolución y el uso de cromoscopia asociado al entrenamiento de los endoscopistas han permitido detectar lesiones neoplásicas de esófago en estadios iniciales. Estos avances resultaron en la expansión de las indicaciones del tratamiento endoscópico curativo en pacientes con carcinoma de células escamosas de esófago. En los últimos años se ha desarrollado en Japón técnicas para la resección endoluminal en bloque de los tumores gastrointestinales precoces, procedimiento denominado disección endoscópica de la submucosa (DES). Inicialmente la DES fue utilizada para tratamiento de tumores gástricos, y apenas más recientemente esta técnica pasó a ser aplicada para tumores de esófago y colorectales.El presente artículo de revisión presenta una descripción detallada de la DES en el manejo de las neoplasias superficiales de esófago, a fin de contribuir para la difusión de este concepto y la incorporación de este procedimiento en Latinoamérica.Endoscopic treatment of early esophageal squamous carcinoma by the endoscopic submucosal disection.

The development of high-resolution endoscopes with chromoendoscopy and the education of endoscopists have enabled the detection of early stage esophageal squamous-cell carcinoma (ESCC). Moreover, in recent years there has been an important progress in the management of early gastrointestinal neoplastic lesions after the development in Japan of endoluminal techniques for en-block tumor resection, namely endoscopic submucosal dissection (ESD). The combination of these factors facilitated the expansion of indications for endoscopic minimally invasive curative interventions in selected patients with superficial ESCC. This review article presents a comprehensive overview and detailed description of the ESD procedure for treatment of ESCC in order to facilitate the dissemination of this concept and the incorporation of this new technique in Latin-America.

VEGF as a Predictor for Response to Definitive Chemoradiotherapy and COX-2 as a Prognosticator for Survival in Esophageal Squamous Cell Carcinoma

We investigated the patterns of pretreatment expression of the epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2) by immunohistochemical staining and determined their correlation with treatment response and survival in 44 patients with esophageal squamous cell carcinoma (ESCC) treated with definitive concurrent chemoradiotherapy (CCRT). The definitive CCRT consisted of a median dose of 54 Gy (range: 40.0-68.4 Gy) and two cycles of concurrent administration of mostly 5-fluorouracil + cisplatinum. High expression of EGFR, VEGF, and COX-2 was found in 79.5%, 31.8%, and 38.6%, respectively. The Cox regression analysis for overall survival (OS) showed that both the treatment response and COX-2 expression were significant. The 3-yr OS rates of patients that achieved a complete response and those that did not were 46.7% and 5.3%, respectively (P = 0.006). The logistic regression analysis for treatment response with various parameters showed that only a high expression of VEGF was significantly associated with a complete response. Unlike other well-known studies, higher expression of VEGF was significantly correlated with a complete response to CCRT in this study. However, higher expression of COX-2 was significantly associated with shorter survival. These results suggest that VEGF might be a predictive factor for treatment response and COX-2 a prognostic factor for OS in patients with ESCC after definitive CCRT.

Terapêutica neo-adjuvante aumenta as complicações pós-operatórias da esofagectomia / Does neoadjuvant therapy increase postoperative complications of esophagectomy

RACIONAL: O câncer de esôfago é o oitavo tipo de câncer mais incidente na população no mundo, sendo que no Brasil são estimados 10.630 novos casos para o ano de 2010. Na terapêutica curativa, a esofagectomia destaca-se nas suas mais diversas modalidades de tratamento. OBJETIVO: Avaliar por meio de um estudo retrospectivo não-randomizado as complicações peri-operatórias dos pacientes submetidos à esofagectomia por carcinoma epidermóide do esôfago, com ou sem terapêutica neo-adjuvante. MÉTODOS: Foram analisados 123 pacientes operados, submetidos na sua maioria (80 por cento) à esofagectomia transmediastinal com anastomose esofagogástrica cervical, assim distribuídos: 81 (65,8 por cento) submetidos à radioterapia neo-adjuvante, 16 (13 por cento) à radioterapia e quimioterapia neo-adjuvantes e 26 (21,2 por cento) à cirurgia exclusiva. RESULTADOS: As principais complicações consideradas foram: hemorragia intra-operatória (4 por cento), pneumotórax / hemotórax (73,1 por cento), broncopneumonia (20,3 por cento) e fístulas e estenose de anastomose (44,7 por cento). Não houve diferenças significativas nas complicações entre os grupos, exceto em relação pneumotórax / hemotórax em que houve menor ocorrência no grupo de cirurgia exclusiva. A mortalidade geral foi de 14 casos (8,8 por cento), não relacionada ao tratamento empregado. CONCLUSÃO: O emprego da terapêutica neo-adjuvante com quimioterapia e radioterapia com a finalidade de obter-se melhor sobrevida e taxas de ressecção completa não resultou em aumento nas complicações peri-operatórias.

BACKGROUND: Esophageal cancer is the eighth most frequent type of cancer in the population in the world, and in Brazil 10.630 new cases are estimated for the year 2010. In curative treatment, esophagectomy stands out in its various treatment modalities. AIM: To assess by means of a retrospective nonrandomized the perioperative complications of patients submitted to esophagectomy for squamous cell carcinoma of the esophagus, with or without neoadjuvant therapy. METHODS: Were analyzed 123 patients operated, undergoing mostly (80 percent) transmediastinal esophagectomy with cervical esophagogastric anastomosis, distributed as follows: 81 (65.8 percent) underwent radiotherapy neo-adjuvant, 16 (13 percent) chemoradiotherapy neoadjuvant and 26 (21,2 percent) to surgery alone. RESULTS: Major complications considered were: intraoperative hemorrhage (4 percent), pneumothorax / hemothorax (73.1 percent), pneumonia (20.3 percent) and fistula and anastomotic stenosis (44.7 percent). No significant differences in complications between the groups, except for pneumothorax / hemothorax in which there was a lower incidence in the group of surgery alone. Overall mortality was 14 cases (8.8 percent), unrelated to the treatment used. CONCLUSION: The neoadjuvant chemoradiotherapy in order to obtain better survival rates and complete resection resulted in no increase in perioperative complications.

Feasibility study of docetaxel, oxaliplatin and capecitabine combination regimen in advanced gastric or gastroesophageal adenocarcinoma

At present, there is no standard regimen for the treatment of gastroesophageal cancer. Docetaxel, cisplatin and fluorouracil [DCF] has been shown to be an effective regimen; however, toxicity is an area of concern in the palliative case setting. Capecitabine and oxaliplatin have been shown to be as effective as fluorouracil and cisplatin, respectively. To reduce the toxicity of DCF while maintaining efficacy, we conducted this study to evaluate the efficacy of docetaxel, oxaliplatin and capecitabine [DOX] combination in advanced gastroesophageal cancer. Patients with histologically confirmed metastatic or locally advanced adenocarcinoma of the stomach or gastroesophageal junction received docetaxel 25 mg/m2 and oxaliplatin 50 mg/m2 on days 1 and 8 with capecitabine 625 mg/m2 twice daily from day 1-14, in 21-day cycles. The primary endpoint was overall response rate [ORR]. Of 21 patients, there were 16 males and 5 females with a median age of 57 years, range 37-80 years. The primary tumor was located at the gastroesophageal junction in 7 patients and in other parts of the stomach in the remaining 14 patients. One patient had locally advanced tumor without distant metastases and 20 patients presented with metastatic disease. Grade 3/4 toxicities included diarrhea [24%], hand-foot syndrome [5%] and febrile neutropenia [5%]. The ORR was 29%. The median survival was 8.4 months. At the time of analysis, 5 of the 21 patients [24%] were alive. The DOX combination is tolerable, active and a promising day-care regimen for advanced gastroesophageal cancer

Aspectos atuais da terapêutica neo-adjuvante no carcinoma epidermóide do esôfago. Revisão da literatura / New aspects of the neo-adjuvant therapy in esophageal squamous cell carcinoma. A review of medical literature

INTRODUÇÃO: O câncer de esôfago é o oitavo tipo de câncer mais incidente na população, com alta letalidade a despeito da melhora do tratamento cirúrgico nas últimas décadas. O carcinoma epidermóide tem maior prevalência em vários países em também no Brasil. Sendo assim, estratégias de tratamento neo-adjuvante tornaram-se objeto de estudo em vários centros mundiais de referência.OBJETIVO: Identificar aspectos atuais da terapêutica neo-adjuvante no tratamento do carcinoma epidermóide do esôfago.MÉTODOS: Revisão bibliográfica de artigos científicos disponíveis no Medline e na base de dados Cochrane cruzando-se os descritores neoplasia esofágicas, cirurgia, quimioterapia, radioterapia.CONCLUSÃO: A estratégia da terapêutica neo-adjuvante é cada vez mais utilizada como forma de oferecer melhores resultados tardios na sobrevida e na qualidade de vida dos pacientes portadores de carcinoma do esôfago.

INTRODUCTION: Esophageal neoplasm is the eighth more prevalent cancer in the general population, with high letality in spite of improvements in surgery in the last decades. The squamous cell carcinoma have higher prevalence in many countries and also in Brazil. Therefore, treatment strategies become target of study in many reference centres around the world.AIM: To identify the new aspects of the neo-adjuvant therapy in the esophageal squamous cell carcinoma.METHODS: Bibliography review of scientific papers available at Medline and Cohchrane Database crossing the following headings: esophageal neoplasms, surgery, drug therapy, radiotherapy.CONCLUSION: Neo-adjuvant therapy is increasingly employed in patients with carcinoma of the esophagus in efforts to improve survival and quality of life of these patients.

Definitive Chemoradiotherapy with Capecitabine and Cisplatin in Patients with Esophageal Cancer: A Pilot Study

We aimed to evaluate the feasibility of concurrent chemoradiotherapy (CRT) with capecitabine and cisplatin in patients with squamous cell carcinoma of the esophagus. Eighteen patients with esophageal cancer were enrolled on the study. The chemotherapy during CRT consisted of two cycles of intravenous cisplatin of 60 mg/ m2 on day 1 and oral capecitabine 825 mg/m2 twice daily from day 1 to 14 at 3-week intervals. The radiotherapy (2.0 Gy fraction/day to a total dose of 60 Gy) was delivered to the primary tumor site and regional lymph node. After concurrent CRT, 2 cycles of capecitabine (1,000 mg/m2 b.i.d from days 1 to 14) plus cisplatin (60 mg/m2 on day 1) were added every 3 weeks. All patients completed the planned treatment. After the chemoradiotherapy, 12 complete responses (CR, 66.7%) and 6 partial responses (PR, 33.3%) were confirmed. Grade 3 or 4 neutropenia only occurred in 2 patients, plus no treatment-related death was observed. At a median follow-up duration of 14.9 months, the estimated overall survival and progression-free survival rate at 2-yr was 70.7% and 54.4%, respectively. Concurrent CRT with capecitabine and cisplatin was found to be well-tolerated and effective in patients with esophageal cancer.

Low-cost outpatient chemotherapy regimen of cisplatin, 5-fluorouracil and leucovorin for advanced head and neck and esophageal carcinomas

CONTEXT AND OBJECTIVE: Patients with advanced head and neck (H/N) and esophageal squamous cell carcinoma (SCC) often have a poor performance status and a dire prognosis. Our aim was to evaluate the feasibility, activity and quality of life (QOL) of an outpatient chemotherapy regimen consisting of cisplatin, 5-fluorouracil and leucovorin (CFL). DESIGN AND SETTING: Prospective phase II study conducted at a Brazilian public institution. METHODS: Fifteen patients with residual, recurrent or metastatic SCC of the H/N or esophagus received bolus infusions of leucovorin 20 mg/m²/day and 5-fluorouracil 370 mg/m²/day on days 1-4, and 90 minutes of infusion of cisplatin 25 mg/m²/day on days 1-3, every 21 to 28 days, depending on hematological recovery. We also evaluated QOL by applying the European Organization for Research and Treatment of Cancer Quality of Life-C30 questionnaire (EORTC QLQ-C30) before each cycle. RESULTS: The overall response rate was 36 percent, and the mean overall survival and progression-free survival were six and three months, respectively. We observed grade 3 or higher hematological toxicity in seven patients and one patient had grade 3 nausea and vomiting. One patient died because of neutropenic fever. Seven out of the 12 patients who could be evaluated regarding QOL presented an improvement in their overall health status and functional QOL scores over the course of the treatment. CONCLUSIONS: CFL is an active outpatient protocol with tolerable toxicity and a favorable QOL impact. Larger studies are warranted, in order to confirm these results.

CONTEXTO E OBJETIVO: Pacientes com carcinoma espinocelular (CEC) de cabeça e pescoço e esôfago frequentemente tem um baixo Karnofsky Performance Status (KPS) e um prognóstico ruim. Nosso objetivo foi avaliar eficácia, taxa de resposta e qualidade de vida nesse contexto, em pacientes tratados com o regime ambulatorial cisplatina, 5-fluoruracil e leucovorin (CFL). TIPO DE ESTUDO: Estudo prospectivo fase II conduzido em uma instituição pública brasileira. MÉTODOS: 15 pacientes com CEC de cabeça e pescoço e esôfago persistente, recorrente ou metastático receberam leucovorin 20 mg/m²/dia, in bolus seguido de 5-fluoruracil 370 mg/m²/dia, in bolus nos dias 1 a 4 e cisplatina 25 mg/m²/dia em infusão de 90 minutos nos dias 1 a 3 a cada 21 ou 28 dias, dependendo da recuperação hematológica. Qualidade de vida foi analisada utilizando o questionário EORTC QLQ-C30, aplicado antes de cada ciclo. RESULTADOS: A taxa de resposta objetiva foi de 36 por cento e a sobrevida global e a sobrevida livre de progressão médias foram de 6,7 e 3,7 meses, respectivamente. Toxicidade hematológica maior ou igual a grau 3 foi observada em sete pacientes e um paciente apresentou náusea e vômito grau 3. Um paciente foi a óbito por neutropenia febril. Sete de 12 pacientes avaliáveis apresentaram melhora no estado geral de saúde e oito nas escalas funcional e sintomática com o tratamento. CONCLUSÃO: CFL é um protocolo ambulatorial factível, com toxicidade aceitável e com impacto favorável na qualidade de vida. Estudos maiores devem ser realizados para confirmar estes resultados.