Results of radiotherapy for inoperable locally advanced esophageal cancer

Three hundred and eleven patients with locally advanced esophageal cancer were treated by radiation therapy from 1968 to 1983 at Tokyo Women's Medical College. Of these, 288 patients with previously untreated, histologically confirmed squamous cell carcinoma but previously treated with curative intent, were eligible for analysis. The cumulative 5-year survival rate of 288 patients given radical radiotherapy was 9.0%. Sex, tumor length, and Stage (AJC) had a great influence on prognosis. The five-year survival rate in males was 5.4% and in females was 22.4%. The five-year survival rate in cases with a tumor length of 5 cm or less was 17.7% in 5-10 cm was 10.0%, and in 10 cm or above was 2.8% and they were 20.2% for Stage I, 9.9% for Stage II, and 2.6% for Stage III. There were no significant differences of survival rate among age, tumor site, and tumor type on X ray film. This data suggests that comparatively early, small-volume tumors share a significant potential for cure by radiotherapy, but potent combined therapy is necessary for the treatment of advanced cancers.     

Choice of fractionation regimen in radiotherapy of inoperable esophageal cancer

The results of definitive radiation treatment for 303 patients with inoperable esophageal cancer were analyzed. Four regimens of fractionation were used: (1) accelerated hyperfractionation (AHF) (70)--1.3 Gy, twice a day, 5 weeks, to a total of 57.2-70 Gy; (2) AHF (49)--1.5-d = 1.5 Gy to a total of 54-63 Gy; (3) AHF (37)--1.7-d = 1.7 Gy to a total of 56.1-57.83 Gy and (4) standard fractionation (SF) (147) to a total of 58-70 Gy. The complete regression rate in the AHF groups (1.3-1.7, 69, 61 and 73%, respectively) was significantly higher than in that of SF (38%) (p(0.01); the median survival in the AHF groups and SF--21, 22, 12.3 and 14.3 months, respectively, and the 5-year survival 14, 12, 4 and 0%, respectively; all the differences in the groups 1.3 and SF were significant. The common independent prognostic factors for all patients were age (p = 0.04), immediate effect of radiation therapy (p = 0.01) and the length of tumor (p = 0.02).     

Combined chemotherapy and radiotherapy in inoperable non-small cell lung cancer

Despite its low efficacy, radiotherapy has traditionally been considered the mainstay of treatment in inoperable stage III NSCLC. One of the attempts to improve the outcome is combining radiation with chemotherapy. This strategy is expected to increase the cure rate not only by improved locoregional tumor control but also by elimination of micrometastases outside the radiotherapy field. Chemotherapy and radiation may be applied in sequence or concurrently. The results of randomized studies testing these two strategies have been inconsistent, however a series of recent trials and the metaanalysis demonstrated a survival benefit of chemoradiation over radiotherapy alone. Recently, concurrent chemotherapy and radiation was found to be superior to sequential application but toxicity of the former is higher. The value of new agents (taxanes, vinorelbine, gemcitabine and topoisomerase inhibitors) in combined modality therapy of NSCLC seems to be promising, but warrants further clinical evaluation.     

Bleomycin infusions combined with radiotherapy in the treatment of inoperable esophageal cancer

A combination of bleomycin, in a 12 h infusion, and radiotherapy was applied in 25 patients with untreated inoperable esophageal cancer. Bleomycin was administered 15 mg/m2 twice weekly, concurrently with irradiation (total dose 3600-4000 rad). Such combined treatment produced 3 complete remissions of the esophageal tumor, 10 partial remissions (response rate 52%--13/25), 3 stable disease cases, while in 9 cases the disease progressed in spite of therapy. The median duration of remissions was 8.7 months in complete responders, 6.0 months in partial responders, and 3.0 months in stable disease cases. Similarly, median survival was the longest in complete remission cases (10.3 months). Patients who did not respond to therapy had a median survival of only 2.8 months. Adverse treatment reactions were of a milder character, except retrosternal pain and burning caused by irradiation mucositis, which occurred in 80% of patients. The trial showed that the combination of bleomycin applied in the form of 12 h infusion and irradiation can produce remissions in 50% of inoperable esophageal cancer cases, i.e., a rate of remission which is similar to that achieved by irradiation and bleomycin applied in the form of rapid (push) i.v. injections.     

Combined radiotherapy and chemotherapy for the treatment of esophageal cancer

Eight patients with esophageal cancer were treated by a new treatment schedule consisting of low dose irradiation, crescendo cisplatin and bleomycin polyacrylate pasta. As monitored endoscopically, therapeutic responses were satisfactory: seven out of 8 patients have survived for a range of 3 to 20 months and still active at work or cancer-free. However, one patient suffered from a second malignancy of adenocarcinoma of the upper esophagus different from the initial squamous cell carcinoma at the lower esophagus which had successfully been treated 3 months before. The present therapeutic design aims at treatment of lymphatic spreads in the adjacent structures as well as the original tumor in the esophagus and submucosal invasions. It is basically a consecutive, multimodal integration of selective concentration of therapeutic effects (extensive radiotherapy, topical application of bleomycin polyacrylate pasta, lymphatic chasing with colloidal bleomycin, and spatial concentration of cisplatin as the result of radiation-induced inflammation), perpetuation of the repairable DNA damage, and biological amplifications (protection against esophageal perforation with polyacrylate coating, and specific cancer cell recruitment). Application of the present therapeutic design is being expanded to the treatment of cancer of other specific sites such as the head and neck tumors and rectal cancer with undeniable prospects.     

Usefulness of esophageal prosthesis in inoperable esophageal cancer

Radiotherapy of inoperable esophageal cancer provided palliation for dysphagia in only 40% of the patients treated over the past 5 years at our hospital. The remaining patients were unable to eat a regular diet even after radiotherapy and to provide them with nourishment, a gastrostomy and/or IVH were required. We feel that the release of the patient from a medical environment will lead to a better quality of remaining life. From our experience with a prosthesis tube for palliation of a malignant esophageal stricture, 4 patients showed excellent results with this way of improving their oral intake.     

同步放化疗治疗不能手术的食管癌临床结果

目的 探讨同步放化疗治疗不能手术的食管癌的近期疗效、生存期及毒性反应.方法 88例食管癌患者根据入选标准随机分组,43例进入放疗＋化疗组（放化组）,45例进入单纯放疗组（单放组）.化疗为第1～4天氟尿嘧啶500mg/m^2＋顺铂20mg/m^2（DF方案）.放疗从第1天即开始,6MVX线三野等中心照射,DT60～65Gy,30～33分次,6.0～6.5周.结果放化组与单放组完全缓解率分别为32.6%、13%（X^2=4.63,P＜0.05）.1、2、3年局部控制率放化组分别为79%、65%、51%,单放组的分别为69%、49%、42%（X^2=3.12,P=0.056）.1、2、3年生存率放化组分别为77%、58%、47%,单放组的分别为67%、42%、38%（X^2=2.27,P=0.132）.放化组毒性反应大于单放组,但患者均能耐受.结论 以DF方案化疗配合放疗不能手术的食管癌近期疗效和局部控制率较好,有提高远期生存率可能,虽毒性反应增加但能耐受.     

食管癌的精确放射治疗

三维适形放疗能提高食管癌放疗的适形性和减少正常组织的照射剂量.所以,笔者在本文中探讨了如何勾画靶区,以及如何在限制肺和心脏等正常组织剂量的同时使得靶区受到较好的剂量分布.     

External beam radiotherapy and intraluminal brachytherapy in advanced inoperable esophageal cancer: JIPMER experience

From January 1994 to September 1998, all inoperable cases of cancer of the esophagus at Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, India were given external beam radiotherapy (EBRT) 36 Gy/18 times by anteroposterior pair. After EBRT, those patients who could be intubated with 16 F Levine's tube either directly or after endoscopic dilatation were given intraluminal brachytherapy (ILBT) 36 Gy in 48 hours at 1 cm. Others were treated by EBRT by posterior oblique fields 24 Gy/12 times. Fifty-eight patients who received EBRT and ILBT formed the study group. Fifty percent had middle one third growth and except for three, all were squamous cell carcinoma (95%). Fifty-nine percent required postradiation endoscopic dilatation. The overall survival rate was 24% at the end of 1 year. In one patient, tracheoesophageal fistula developed 4 months after treatment. Mild-to-moderate acute esophagitis developed in 10% of the patients, and 2% had slight hemoptysis, but these were not significant enough to interrupt treatment. There was no treatment-related mortality. Thirty-four patients (59%) were followed up for 6 months to 5 years (mean, 9.6 months). Three patients had follow-up of more than 3 years with no evidence of disease. EBRT with ILBT, with intermittent esophageal dilatations as required, offers very good palliation in advanced inoperable cancer of the esophagus.     

Combined treatment of inoperable stomach cancer

The results of combination therapy of 66 patients with inoperable gastric cancer are presented. The complex of therapeutic measures included: preoperative gammatherapy with a single dose of 350--400 rad and total dosage up to 2400--3000 rad, palliative operations or explorative laparotomy with subsequent postoperative irradiation (up to 4500--6000 rad) or chemotherapy with 5-fluoruracil (up to 3--5 grams). The average survival of patients was 9.3 +/- 0.9 months, and it was dependent on tumor process spread and the kind of surgical intervention. Radiotherapy is shown to effect positively the clinical course of the disease and patient's survival.     

Multiple fraction per day radiation therapy for inoperable esophageal cancer

Experience with a multiple fractions per day radiation therapy program for inoperable esophageal cancer is reported. The treatment program consisted of 3 daily fractions of 1.6 Gy, with a 4 hr interval between fractions, for 5 consecutive days (24 Gy). After a rest period of 2 weeks, a second course of radiation was given with the same dose and fractionation for a total dose of 48 Gy in an overall treatment time of 4 weeks. Thirty-four patients were treated between February 1981 and July 1983. Acute reactions consisted of mild esophagitis noted in 30% of patients. No treatment related complications were reported. Median survival was 7 months and the 2- and 5-year survival rates were 12 and 9%, respectively. Tumor size and Karnofsky performance status were found to be the most important prognostic indicators for prolonged survival. Prompt palliation of symptoms was noted. Thirty-three per cent of patients had complete resolution and 41% had partial improvement of symptoms after completion of treatment. Four patients (12%) obtained complete tumor regression with negative biopsy at endoscopic examination and 2 of them are free of disease at 58 and 64 months. A partial response was reported in 12 patients (35%) for a median duration of 5 months (3-26). Treatment with multiple fractions per day was feasible in patients with esophageal cancer and could be preferred to more conventional fractionations for promptness of palliation and the shorter treatment time. The expected therapeutic gain is discussed.     

Safety and efficacy of concurrent cisplatin and radiotherapy in inoperable or metastatic squamous cell esophageal cancer

Between August 1996 and May 1999, 50 consecutive, previously untreated patients with carcinoma of the esophagus and who were inoperable for various reasons were treated with weekly doses of cisplatin (35 mg/m 2 , maximum 7 cycles) concurrent with either 66 Gy/33 fractions external beam radiotherapy (EBRT) (n=42) or 50 Gy/25 fractions EBRT and two insertions of high-dose-rate intraluminal radiotherapy of 6 Gy each, spaced a week apart (n=8). Eighty-two percent (41/50) of the patients received the stipulated radiotherapy (RT) dose. Seventy-six percent (38/50) received at least 6 cycles of chemotherapy. Neutropenia in the form of WHO grade II-12% (6/50) and grade III-2% (1/50) was observed. Grade III emesis was seen in 8% (4/50). Improvement in the swallowing status was seen in 84% (42/50). Median duration of dysphagia relief was 6 months. The median overall survival was 9 months with 17% estimated to be alive after 4 years. Combined treatment with single agent cisplatin and definitive radiotherapy for inoperable cancer of the esophagus is safe, well tolerated and reasonably efficacious.     

外照射放疗联合腔内近距离放疗治疗食管癌的系统评价

目的:评价外照射联合腔内近距离放疗(观察组)与单纯外照射放疗(对照组)治疗食管癌的疗效和安全性.方法:通过计算机检索CBMdisc、VIP、CNKI、Cochrane Library、Pubmed和Embase等数据库和手工检索8种主要中文肿瘤学期刊,收集有关外照射联合腔内近距离放疗与单纯外照射放疗治疗食管癌的随机和半随机对照试验.采用RevMan 4.2.10进行统计学分析.结果:共收集到14个已发表的随机对照试验,1 400例患者,方法学质量评价均为C级.Meta分析结果显示,近期有效率,1和3年生存率明显高于单纯外照射放疗,局部复发率在观察组降低,P值分别为0.03、＜0.000 01、0.005和0.02;两组5年生存率及远处转移率相似,P值分别为0.29和0.43;观察组放射性食管炎、出血、良性食管狭窄的发生率高于对照组,P值分别为0.04、0.002和0.03.两组食管穿孔和食管溃疡的发生率差异无统计学意义,P值分别为0.77和0.20;放射性肺炎发生率对照组高于观察组,P=0.000 5.结论:与观察组相比,治疗组近期、1和3年生存率提高,局部复发降低;但远期生存率及远处转移率无改善;治疗组不良反应发生率增加.     

同步放化疗治疗不能手术的食管癌疗效分析

目的 :不能手术的食管癌同步放化疗的疗效观察。方法 :88例食管癌患者根据入选标准随机分组 ,4 3例进入化疗 +放射治疗组 (放化组 ) ,4 5例进入单纯放射治疗组 (单放组 )。放化组 :化疗为DF方案 ,即 5 Fu 5 0 0mg/m2 d1～d4 ,DDP2 0mg/m2 d1 d4 ;放射治疗从第 1天即开始 ,6MV x射线照射 ,三野等中心照射DT 6 0GY 6 5GY/30 33Fr/6 6 5W。单放组 :放射治疗方案同综合组。结果 :放化组的 12个月、2 4个月生存率分别为 76 7%、5 8 1% ,单放组的 12个月、2 4个月生存率分别为 6 6 7%、4 2 2 % ,但二组间的生存率统计学上未显示出统计学差异 (χ2 =2 2 7,P =0 132 )。放化组的 2年远处转移发生率为 16 3% ,低于单放组的 2 8 9% (P <0 0 5 )。放化组的毒性反应大于单放组 ,但患者均能耐受。结论 :以DF方案化疗配合放射治疗不能手术的食管癌降低了远处转移发生率 ,同时有提高远期生存率的可能性 ,虽毒性反应增加 ,但患者均能耐受 ,有进一步研究的价值     

Combined modality treatment using concurrent radiotherapy and pharmacologically-guided carboplatin for inoperable and incompletely resected non-small cell lung cancer

BACKGROUND: In our previous randomised trial, radiotherapy (RT) was given concurrently with carboplatin 350 mg/m(2). We wanted to show that the safety and efficacy of the drug could be improved by pharmacologically-guided dosing based on renal function. PATIENTS AND METHODS: Patients were eligible if they had unresectable or incompletely resected NSCLC, good performance status (ECOG 0-2), weight loss < 10%, no distant metastases and adequate haematology and biochemistry. Radiotherapy was given to the primary site and regional lymph nodes to a total dose of 60 Gy in 30 fractions over 6 weeks. Two cycles of carboplatin were given in divided doses of 1-h infusions daily for 5 days before RT weeks 1 and 6. A total plasma AUC of 7 mg/ml per minute per cycle was targeted. The total dose was calculated by using Calvert or Chatelut formulae. RESULTS: Forty-nine patients were treated. Patient characteristics included: 78% male; mean age 66 (range: 38--78); 80% stage 3A or 3B; incomplete resection in six patients. The median dose of carboplatin administered per cycle was 850 mg (range 435--1650); 89% of patients received a higher carboplatin dose compared with BSA-calculated dose (mean increase 41%). Forty-two patients (86%) completed treatment as planned. Myelosuppression > or = grade 3 occurred in 14 patients (29%) (one patient died of pneumonia while neutropenic); two patients developed > or = grade 3 acute oesophagitis and two patients had > or = grade 3 acute pulmonary toxicity. Late pulmonary toxicity > or = grade 3 occurred in two patients. The mean potential follow-up time was 2.7 years. The estimated proportion of patients alive and free of local or distant progression at 1 year was 42% and the median survival duration was 16 months (95% CI: 11--21 months). CONCLUSIONS: Radical chest irradiation can be combined with two cycles of pharmacologically-guided full-dose carboplatin, however because our study demonstrated significant haematologic toxicity, we recommend carboplatin dosing according to renal function at less than full dose (i.e. AUC 6 mg/ml per minute per cycle).