Chemoradiation in conservation therapy for esophageal cancer

Irradiation alone can be highly beneficial for patients with advanced or metastatic esophageal cancer, but external beam irradiation alone is now usually reserved for patients only requiring palliation. Higher cure rates are achieved with irradiation delivered with radiosensitizing chemotherapy based on clinical trials performed over the last decade. Chemoradiation programs based on the modest success with infusional 5-FU, cisplatin, and 50 Gy are justified for either palliative or curative treatment as long as the toxicity is acceptable. One challenge is to increase the incidence of pathologic complete response rates without incurring unacceptable acute toxicity, which is the major dose-limiting factor in current trials. Newer methods that may ameliorate acute injury are different dose schedules for chemoradiation and different methods of dose delivery. Infusional administration of chemotherapy and new dose planning and delivery systems for irradiation (conformal irradiation) are currently under study. Organ preservation for larger numbers of patients may be possible if any of these methods hold up to the early indications of success.     

Chemoradiation is a tolerable therapy for older adults with esophageal cancer

INTRODUCTION: Esophageal adenocarcinoma (EC) is increasing in incidence. Chemoradiation (CRT) is regarded as an acceptable alternative to surgery for the management of locally advanced EC. Ten-20% of EC patients are over the age of 75 years. There are limited data regarding efficacy and tolerability of CRT for the treatment of EC in the elderly. PATIENTS AND METHODS: We retrospectively reviewed EC cases > or = 70 years of age treated with CRT at a single institution. Clinical data, regarding therapy administered and outcome, were obtained from records. Clinical prognostic variables were analyzed against survival in a univariate model using the log rank test and in a multivariate model using Cox proportional hazards analysis. RESULTS: Thirty consecutive patient records were identified. Commonly used chemotherapy agents included 5-fluorouracil, cisplatin, paclitaxel and oxaliplatin. There was no significant correlation between age and survival. The dose of chemotherapy or radiation was unrelated to any of the toxicities (p-values > 0.16). The most common grade 3 or 4 toxicities were dehydration, hypotension, mucositis and pneumonitis. On multivariate analysis, adenocarcinoma histology (p = 0.0094) and higher radiation dose (p = 0.0158) were associated with improved survival. The median survival of the patients was 10 months. CONCLUSION: CRT was tolerable for older patients with EC. Close monitoring for dehydration, nutritional compromise and pulmonary toxicity is required.     

Chemoradiation therapy for stage IV pancreatic cancer

BACKGROUND: Pancreatic cancer is a malignant tumor with a poor prognosis. It frequently presents with locally advanced and distant metastasis at the time of diagnosis. Favorable results were obtained by performing intraoperative radiation therapy (IORT) and chemotherapy (administration of GEM) for the treatment of inoperable pancreatic cancer. A study was conducted on its efficacy as an adjuvant therapy for inoperable and advanced pancreatic cancer. SUBJECTS AND METHODS: Between May 1998 and December 2002, 40 patients with stage IV pancreatic cancer were treated at our institution. The study comprised background factors, adjuvant therapy and survival rate. RESULTS: According to the treatment modality, the study population was classified into four groups: group A, consisting of 3 patients with localized unresectable tumors who had been treated with IORT: group B, 5 patients who underwent curative resection of primary tumor combined with IORT: group C, 6 patients who were administered GEM combined with IORT: group D, 26 patients not falling into groups A, B or C. The mean survival for group A, B, C and D was 10.3 months, 6.7 months, 16.8 months and 9.4 months, respectively. The 1-year survival rates were 0%, 0%, 80.0% and 19.3%, respectively. The mean survival and the 1-year survival rate were significantly better in group C than in the other groups. In group C, the tumor decreased in size, invasion of large vessels and pancreatic posterior evolution was suppressed, and 4 patients survived for 17 months or more. CONCLUSIONS: Prolongation of the survival period was shown by concomitant IORT and administration of GEM for inoperable advanced pancreatic cancer. Thus, attempting to combine chemotherapy with IORT and giving additional consideration to the administration method was shown to provide adjuvant therapy that can be expected to be effective against stage IV inoperable pancreatic cancer.     

Chemoradiation therapy for advanced esophageal cancers--report of 3 cases]

Three cases of prominent-type advanced esophageal cancer were treated with chemoradiation therapy using a 5-FU analog and low dose CDDP. All cases showed a complete response after the treatment. Only mild bone marrow suppression was found in one case. This protocol will be applied for patients with prominent-type advanced esophageal cancers, especially high risk patients.     

Chemoradiation therapy of inoperable lung cancer]

The results of utilization of different variants of the complex therapy in 416 patients with inoperable lung cancer are reported. 5-fluoruracil, cyclophosphan, methotrexate, chrysomallin were employed as antitumor drugs. Radiotherapy was carried out on a distance gamma machine. The best immediate and early results were gained in patients treated by distance gammatherapy against the background of cyclophosphan injections. The results proved to be most favourable within the terms of 3 years and longer in case of gammatherapy associated with 5-fluoruracil. Application of a fractionated radiation course rendered no positive effect on the results of treatment.     

Multimodality therapy for esophageal cancer

Recent developments in the epidemiology, staging, and treatment of esophageal and gastroesophageal junction cancers have led to significant changes in the way these malignancies are managed. Although a relationship between gastroesophageal reflux disease and esophageal cancer has been demonstrated, antireflux surgery has been shown to have no preventive effect with regard to the development of esophageal adenocarcinoma. The newly modified staging system of the World Esophageal Cancer Consortium has helped define the optimal number of lymph nodes to dissect during an esophagectomy. Incorporating modern techniques, such as esophageal ultrasound, fine needle aspiration, and positron emission tomography, can improve the prognostic value of staging. Use of higher-volume centers and higher-volume surgeons for the performance of procedures in upper gastrointestinal cancers is associated with better outcomes. Neoadjuvant chemoradiation using a wide variety of chemotherapy regimens appears to have become the new standard of care for stage II and III esophageal cancer.     

Second-line therapy for esophageal cancer

Esophageal cancer is a highly lethal disease, with most patients presenting with unresectable or metastatic disease. Since metastatic esophageal cancer is an incurable disease, the goals for chemotherapy are to palliate symptoms and improve survival. Although some patients may achieve symptomatic improvement with the use of standard first-line chemotherapy regimens, response rates are usually low and short lasting. Virtually all patients with metastatic esophageal cancer will develop progressive disease following front-line therapy. With the availability of several chemotherapeutic agents with more tolerable side effects, a number of patients who retain a good performance status after the initial treatment remain candidates for additional therapy. This review summarizes the recent advances in second-line therapy for esophageal cancer.     

Neoadjuvant therapy for esophageal cancer

Esophageal cancer is increasing in incidence more than any other visceral malignancy in North America. Adenocarcinoma has become the most common cell type. Surgery remains the primary treatment modality for locoregional disease. Overall survival with surgery alone has been dismal, with metastatic disease the primary mode of treatment failure after an R0 surgical resection. Cure rates with chemotherapy or radiation therapy alone have been disappointing as well. For these reasons, over the last decade multi-modality treatment has gained increasing acceptance as the standard of care. This review examines the present data and role of neoadjuvant treatment using chemotherapy and radiation therapy followed by surgery for the treatment of esophageal cancer.     

Combined modality therapy for esophageal cancer

Whereas many patients with esophageal carcinoma present with what appears to be localized disease, cure rates with surgical resection alone remain low. Although surgical resection, where feasible, affords patients the best chance of cure, the primary tumor has often invaded local tissues or structures, and occult micrometastases often exist at the time of presentation. In an effort to improve treatment results, various combinations of surgery, radiotherapy, and chemotherapy have been used. The results of combined modality therapy are reviewed in this article. The importance of accurate pretreatment staging is discussed, and ongoing prospective randomized trials are reviewed.     

Primary combined-modality therapy for esophageal cancer

Based on positive results from the Radiation Therapy Oncology Group (RTOG) 85-01 trial, the conventional nonsurgical treatment of esophageal carcinoma is combined-modality therapy. Dose intensification of the RTOG 85-01 regimen, examined in the Intergroup (INT)-0123/RTOG 94-05 trial, did not improve local control or survival. Areas of clinical investigation include the development of combined-modality therapy regimens with newer systemic agents, the use of 18F-fluorodeoxyglucose positron-emission tomography to assist in the development of innovative radiation treatment planning techniques, and the identification of prognostic molecular markers. The addition of surgery following primary combined-modality therapy apparently does not improve survival, but this finding is controversial.     

食管癌靶向治疗研究进展

2012年报告显示食管癌发病率在全球恶性肿瘤中居第5位,死亡率居第4位,与往年数据统计相比,其发病率及死亡率均呈上升趋势。目前对食管癌的治疗已进入多学科综合治疗时代,其中分子靶向治疗也成为研究热点,表现为靶向药物呈现多样化,由单一靶点走向多靶点化,应用于大量Ⅱ~Ⅲ期临床研究中。现今,在食管癌治疗中研究较多的靶向药物主要包括西妥昔单抗、厄罗替尼、曲妥珠单抗、贝伐单抗等。本文通过总结近几年国内外文献资料,对食管癌分子靶向治疗做一综述。     

Chemoradiation for resectable gastric cancer

The incidence of gastric cancer has been declining in recent years, however, the disease continues to be a worldwide public health problem. About two thirds of patients with gastric cancer undergo surgical resection with curative intent. R0 resection--complete local-regional tumour removal with negative resection margins--is the only curative modality. The optimum extent of lymph-node dissection (D1 vs D2) is controversial. Disease relapse, both local and distant, is common and the 5-year survival rate is disappointing. Adjuvant chemotherapy has been studied extensively in this setting but an effective regimen has not yet been identified. A recent intergroup study has shown that postoperative chemoradiation is effective in improving both disease-free survival (3-year, 48% vs 31%, p<0.001) and overall survival (3-year, 50% vs 41%, p=0.005) compared with surgery alone. Preoperative radiation as a single adjuvant therapy has also yielded improvements in local-regional control, disease-free survival, and overall survival compared with surgery alone. Preoperative chemotherapy or chemoradiation has been accepted to have a theoretical advantage over postoperative therapy and has now been shown to be a feasible option. Its efficacy, however, remains to be tested.     

Novel molecular targeted therapy for esophageal cancer

Esophageal cancers are highly lethal neoplasms which are generally refractory to conventional multidisciplinary interventions. Recent elucidation of the mechanisms of esophageal carcinogenesis, as well as preclinical studies utilizing chromatin remodeling agents and inhibitors of oncogene signaling in conjunction with conventional chemotherapeutic agents provide new opportunities for the development of potentially efficacious molecular targeted therapies for these malignancies.     

高发区食管癌的早期基因治疗和预防

目的 将治疗大鼠骨髓增生异常综合征(MDS)和红白血病所用的V-erbB反基因寡核苷酸(ODN,B1和B2)粉针剂应用于高发区食管癌早期和食管原位癌患者的基因治疗.方法 应用两种治疗方案,即第1方案(B1+B2)和第2方案(B1+B2+CpG),分别对41例食管上皮非典型增生(中度增生15例,重度增生26例)及5例食管原位癌患者,在内窥镜下进行局部喷洒药物治疗,隔日1次,连续3次为1个疗程.1～2个月后复查和病理检查.并于治疗后5年进行随访复查.结果 41例食管上皮非典型增生患者应用第1方案治疗,其中33例从中度增生或重度增生逆转为轻度增生或正常,有效率为80.5%.8例无效,其中1例进展为原位癌.第2方案治疗5例原位癌,3例有效(1例逆转为重度增生.1例逆转为轻度增生,1例逆转为轻度食管炎),2例无效.治疗后5年随访,84.2%患者已痊愈.结论 上述两个治疗方案对高发区癌症的二级预防意义重大.     

Radiation therapy for limited-stage small-cell esophageal cancer

Between 1985 and 1999, 20 patients with limited-stage small-cell carcinoma of the esophagus (SCEC) received radiation therapy at Tohoku University Hospital and Miyagi Cancer Center Hospital. Twelve patients received definitive radiation therapy and eight patients received postoperative prophylactic irradiation after surgery. The 1-, 2-, and 5-year survival rates of all cases were 44%, 37%, and 19%, respectively. Distant metastasis was the most frequent pattern of recurrence. Survival rates differed significantly between the 6 patients who were not treated with chemotherapy (median survival time, 5 months) and the 14 patients who were (24 months) (p = 0.0061). Good local control rates can be obtained by definite or postoperative radiation therapy for SCEC. However, SCEC should be regarded as a systemic disease, and chemotherapy should be given. Multiinstitutional studies are needed to obtain sufficiently large populations for investigation and optimization of local therapy for this disease.     

Chemoradiation induces epithelial-to-mesenchymal transition in esophageal adenocarcinoma

Multimodality treatment has advanced the outcome of esophageal adenocarcinoma (EAC), but overall survival remains poor. Therapeutic pressure activates effective resistance mechanisms and we characterized these mechanisms in response to the currently used neoadjuvant treatment against EAC: carboplatin, paclitaxel and radiotherapy. We developed an in vitro approximation of this regimen and applied it to primary patient-derived cultures. We observed a heterogeneous epithelial-to-mesenchymal (EMT) response to the high therapeutic pressure exerted by chemoradiation. We found EMT to be initiated by the autocrine production and response to transforming growth factor beta (TGF-β) of EAC cells. Inhibition of TGF-β ligands effectively abolished chemoradiation-induced EMT. Assessment of TGF-β serum levels in EAC patients revealed that high levels after neoadjuvant treatment predicted the presence of fluorodeoxyglucose uptake in lymph nodes on the post-chemoradiation positron emission tomography-scan. Our study shows that chemoradiation contributes to resistant metastatic disease in EAC patients by inducing EMT via autocrine TGF-β production. Monitoring TGF-β serum levels during treatment could identify those patients at risk of developing metastatic disease, and who would likely benefit from TGF-β targeting therapy.     

食管癌靶向治疗的研究进展

近年来手术及放化疗在食管癌治疗方面取得了一定的进步,但中晚期食管癌的长期生存率未见明显提高。目前,分子靶向治疗已成为食管癌的研究热点。     

Immunocorrective therapy in esophageal cancer

Additional non-specific therapy including levamisole and other drugs was tested in 20 patients with esophageal cancer. Complex (immuno- and chemoradiation) treatment brought immune response, lipid metabolism and cortisol level to normal, which in most cases, was in correlation with the clinical effect of therapy.     

Radiation therapy of esophageal cancer

Radiation therapy has been used extensively in the management of patients with cancer of the esophagus. It has demonstrated an ability to cure a small minority of patients. Cure is likely to be limited to patients who have lesions less than 5 cm in length and have minimal, if any, involvement of lymph nodes. Esophagectomy is likely to cure a similar, small percentage of patients with the same presentation of minimal disease but has a substantial acute postoperative mortality rate and greater morbidity than irradiation. Combining surgery and either preoperative or postoperative irradiation may cure a small percentage of patients beyond the number cured with either modality alone. Radiation has demonstrated benefit as an adjuvant to surgery following the resection of minimal disease. However, radiation alone has never been compared directly with surgery for the highly select, minimal lesions managed by surgery. Radiation provides good palliation of dysphagia in the majority of patients, and roughly one third may have adequate swallowing for the duration of their illness when "radical" doses have been employed. Surgical bypass procedures have greater acute morbidity but appear to provide more reliable, prolonged palliation of dysphagia. They constitute the best approach for patients with persistent or recurrent dysphagia following esophageal irradiation. Several approaches to improving the efficacy of irradiation are currently under investigation. Fewer large fractions appear to be equivalent to conventionally fractionated radiotherapy in terms of local control and survival but produce more prompt palliation and shorten courses of palliative therapy. Multiple-daily-fractionation schedules and hyperfractionation have theoretical appeal and clear basis for investigation from the early suggestions of improved response rates in advanced squamous-cell cancer of the head and neck. Hypoxic-cell radiosensitizers, neutron-beam, and helium-ion therapy results have not been overly encouraging in esophageal cancer, thus far. However, the new generation of particle beams and the new radiation-sensitizer drugs require further evaluation. Better means of dealing with the high incidence of disseminated disease are clearly needed. It is clear that combined-modality approaches using both local and systemic therapy will ultimately be desirable in esophageal-cancer treatment.(ABSTRACT TRUNCATED AT 400 WORDS)