Curative radiotherapy with high-dose-rate brachytherapy boost for localized esophageal carcinoma: dose-effect relationship of brachytherapy with the balloon type applicator system.

BACKGROUND AND PURPOSE: This study analyzed the feasibility, local control and toxicity in potentially curable patients with esophageal carcinoma treated with a combination of external irradiation and high-dose-rate (HDR) brachytherapy using a balloon type applicator system to minimize hot spots on the mucosa. MATERIALS AND METHODS: During the 9 years, 124 patients with esophageal carcinoma and no apparent extraesophageal spread were treated with 40-60 Gy of external irradiation followed by 8-24 Gy of HDR brachytherapy. The fraction size of brachytherapy was 4-6 Gy. We developed a new applicator with 15 mm external diameter inflatable balloons. The reference point was a point 12.5 mm depth from the mid source. The study end points were local control, late toxicity and palliative effect. RESULTS: All 124 patients completed the planned radiotherapy. Local control rate was 69/124 (56%). There was a trend toward better local control rate for T1 lesions with increasing dose via brachytherapy. Of 69 patients with local control, treatment-related ulcers occurred in 28 patients, leading to death in four. The incidence of ulcers increased with increasing brachytherapy dose; 1/6 with 12 Gy, 16/43 with 16 Gy, 6/ 12 with 20 Gy, 4/5 with 24 Gy. Esophageal benign strictures occurred in ten patients and in all cases developed from ulcers. The incidence of freedom from dysphagia was not dose-dependent. CONCLUSION: A combination of external irradiation and HDR brachytherapy with the balloon type applicator was feasible and well tolerated. Although better local control was achieved by a higher dose of brachytherapy, the higher dose caused more severe esophageal injury.     

External beam radiation therapy with or without high-dose-rate intraluminal brachytherapy for patients with superficial esophageal carcinoma.

BACKGROUND: Clinical results of external beam radiation therapy (RT) with or without intraluminal brachytherapy (IBT) for patients with superficial esophageal carcinoma were evaluated retrospectively. METHODS: Between 1985 and 1996, 21 patients with superficial esophageal squamous cell carcinoma were treated by external beam RT, with or without high dose rate IBT, with curative intent. There were 18 males and 3 females; their median age was 67 years (range, 51-85 years). Eight patients were treated by external beam RT alone (60-69 gray [Gy]), whereas the remaining 13 patients were treated by IBT after external beam RT. Most patients in the IBT group received 2 or 3 fractions of IBT of 4 Gy after external beam RT of 50-56 Gy. RESULTS: All of the 21 tumors showed complete regression at the end of RT. Local recurrence was noted in 4 patients in the group that received external beam RT alone and in 2 patients in the IBT group. Salvage therapy was successful for 4 patients. Local control probability and cause specific survival probability for the IBT group were significantly higher than those for the group that received external beam RT alone (P < 0.05 for both). The 3-year local control and cause specific survival rates for the IBT group were 85% and 100%, respectively, whereas those for the external beam RT group were 45% and 67%, respectively. Transient esophageal ulcers were noted in two patients in the IBT group. CONCLUSIONS: External beam RT and IBT is a safe and effective treatment modality for patients with superficial esophageal carcinoma.     

长春瑞滨联合参芪扶正注射液同步放疗治疗老年食管癌30例临床观察

目的 观察长春瑞滨联合参芪扶正注射液同步治疗老年食管癌的疗效及其不良反应。方法 60例老年食管鳞状细胞癌患者随机分为单纯放疗组（简称RT组）30例和长春瑞滨联合参芪扶正注射液同步放疗组（简称CRT组）30例,CRT组放疗剂量每28～30次（50.4～54.0）Gy;RT组放疗剂量每35～37次（63.0～66.6）Gy。结果CRT组和RT组患者的有效率分别为96.67%和80.00％,差异有统计学意义(P=0.044)。CRT组患者的中位生存期为23.0月,RT组患者的中位生存期为16.5月。CRT组和RT组患者的3年生存率分别为33.33％和10.00％,差异有统计学意义(P=0.028)。CRT组和RT组患者的不良反应发生率无显著差异。结论 CRT组较RT组有更好的有效率和长期生存率,且不良反应并未增加。对于老年食管癌患者,可采用长春瑞滨联合参芪扶正注射液同步放疗的治疗方法,以期获得更好的疗效及长期生存。     

内外照射加化疗联合治疗食管癌临床分析

目的 分析外照射、腔内近距离治疗及化疗治疗食管癌的疗效及其与外照射比较。方法 １２０例食管癌随机分成４组,每组３０例。Ⅰ组为外照射,Ⅱ组为外照射加腔内照射,Ⅲ组为外照射加化疗,Ⅳ组为内照射加化疗。外照射采用＾６０Ｃｏ治疗,２Ｇｙ／次,５次／周,总剂量６０－７４Ｇｙ;腔内照射６－８Ｇｙ／次,１次／周,总量１８～２４Ｇｙ;化疗用卡铂,１００ｍｇ／ｄ,５次／周,总量１０００ｍｇ。结果 Ⅱ～Ⅳ组的１,２,３年生存率高于Ⅰ组（Ｐ〈０．０５）。Ⅰ～Ⅳ组的３年生存率分别为１３．３％、３６．７％、４０．０％和４６．７％,死于肿瘤复发及未控分别为７２．２％、４０．０％、４３．７％和３８．４％（Ｐ〈０．０５）,远处转移率无明显差异。结论 外照射与近距离治疗和化疗的综合治疗可提高食管癌局部控制率和１,２,３年生存率。     

Multi-institutional randomized trial of external radiotherapy with and without intraluminal brachytherapy for esophageal cancer in Japan. Japanese Society of Therapeutic Radiology and Oncology (JASTRO) Study Group.

PURPOSE: With the aim of improving the results of treatment of esophageal cancer, we designed this multi-institutional, randomized trial to establish the optimal irradiation method in radical radiation therapy for esophageal cancer by clinically evaluating external irradiation alone and in combination with intraluminal brachytherapy. METHODS AND MATERIALS: The study population consisted of patients with squamous cell carcinoma who were expected to be successfully treated with radical radiation therapy. The patients who could be given intraluminal brachytherapy at the end of external irradiation of 60 Gy were stratified into 2 groups. Patients assigned to receive external irradiation alone received boost irradiation of 10 Gy/week on a schedule similar to the previous one, and with the same or smaller irradiation field. Intraluminal brachytherapy was performed, as a rule, with the reference dose point set at a depth of 5 mm of the esophageal submucosa, and a total of 10 Gy was irradiated at a daily dose of 5 Gy, on a once-weekly schedule with low-dose-rate or high-dose-rate brachytherapy equipment. RESULTS: A total of 103 patients were registered, 94 of whom were analyzable, with 8 ineligible, and 1 for whom complete information was unavailable. The overall cumulative survival rate was 20.3% at 5 years. The cause-specific survival rate was 31.8% at 5 years. The cause-specific survival rate at 5 years was 27% in the external irradiation alone group and 38% in intraluminal brachytherapy combined group. There was no significant difference between the 2 groups (p = 0.385). However, in the patients with 5 cm or less tumor length, the cause-specific survival rate was 64% at 5 years in the intraluminal brachytherapy combined group, which showed a significant improvement over 31.5% in the external irradiation alone group (p = 0.025). In the patients with Stage T1 and T2 disease, cause-specific survival rates tended to be better in the intraluminal brachytherapy combined group than in the external irradiation alone group (p = 0.088). In the patients with more than 5 cm tumor length or Stage T3-4 disease, there were no significant differences between the two groups by treatment methods (p = 0.290). The incidence of early and late complications did not differ according to whether intraluminal brachytherapy was used. CONCLUSION: For the purpose of establishing the usefulness of intraluminal brachytherapy, further prospective randomized studies are necessary to evaluate the efficacy in tumors with short length and those with shallow invasion, or to assess the usefulness of intraluminal brachytherapy, as additional irradiation in large advanced tumors have been shown to have disappeared by diagnostic imaging after chemoradiotherapy with 60 Gy/6w external irradiation.     

放化疗联合治疗中晚期食管癌的疗效观察

目的 观察放化疗联合治疗中晚期食管癌的疗效及预后的相关因素.方法 回顾性分析60例中晚期食管癌患者,根据治疗方法 不同分为单纯放疗组(简称单放组)32例和放疗加化疗组(简称放化组)28例.放射治疗均采用6MV-X线常规照射,常规分割2 Gy/次,总量DT60～70 Gy,放化组在放射治疗同时或者放疗后给予顺铂(DDP)加亚叶酸钙(CF)加5-氟尿嘧啶(5-Fu)方案化疗.结果 放化组与单放组1、2、3年生存率分别为73.30%、46.70%、16.67%和60.30%、16.67%、6.67%;其中2年生存率放化组明显高于单放组,差异有统计学意义(P＜0.05).同期放化组与序贯放化组1、2、3年生存率分别为88.89%、55.55%、22.22%和84.21%、47.37%、15.79%.患者近期不良反应,放化组较单放组有所加重,差异有统计学意义(P＜0.05).治疗方式和临床分期是食管癌预后的影响因素(P＜0.05),放化联合较单纯放疗预后好,分期越晚预后越差.结论 放化疗联合能提高中晚期食管癌患者的2年生存率,患者近期不良反应可以耐受,是治疗中晚期食管癌有效的方法 之一.     

Acute esophageal toxicity in non-small cell lung cancer patients after high dose conformal radiotherapy.

BACKGROUND AND PURPOSE: To correlate acute esophageal toxicity with dosimetric and clinical parameters for non-small cell lung cancer (NSCLC) patients treated with radiotherapy (RT) alone or with chemo-radiotherapy (CRT). PATIENTS AND METHODS: We analyzed the data of 156 patients with medically inoperable or locally advanced NSCLC. Seventy-four patients were irradiated with high dose RT only, 45 patients with sequential CRT (Gemicitabine/Cisplatin) and 37 patients with concurrent CRT (Cisplatin daily 6 mg/m(2)). The radiation dose delivered ranged from 49.5 to 94.5 Gy (2.25-2.75 Gy per fraction) with an overall treatment time of 5-6 weeks. For all patients the maximal acute esophageal toxicity (RTOG/EORTC criteria) was scored and related to dose-volume parameters, as well as to clinical and treatment-related parameters. All parameters were tested univariable and multivariable in a binary logistic regression model. The toxicity data of a homogeneous subgroup was fitted to the Lyman-Kutcher-Burman model. RESULTS: Grade 2 acute esophageal toxicity or higher occurred in 27% (n=42) of the patient population of which nine patients developed grade 3 toxicity and one patient grade 4. All 10 patients with grade>or=3 esophageal toxicity received concurrent CRT. At multivariable analysis, the most significant clinical parameter to predict acute esophageal toxicity was the concurrent use of CRT. The most significant dosimetric parameter was the esophagus volume that received at least 35 Gy. The data of the patients who did not receive concurrent CRT were well described by the Lyman-Kutcher-Burman normal tissue complication probability model. The optimal fit of the data of non-concurrent treated patients to this model was obtained using the following values for the parameters: TD(50)=47 Gy (41-60 Gy), n=0.69 (0.18-6.3) and m=0.36 (0.25-0.55) where the numbers between brackets denote the 95% confidence interval. Acute esophageal toxicity was not significantly increased for patients treated with sequential CRT. CONCLUSION: Both concurrent CRT and the volume that receives at least 35 Gy were predictors of acute esophageal toxicity.     

Treatment results of chemoradiotherapy for clinical stage I (T1N0M0) esophageal carcinoma

PURPOSE: In 1991, we started a clinical prospective trial for operable esophageal carcinoma, foreseeing organ preservation, to assess the treatment results after definitive chemoradiotherapy (CRT) for clinical Stage I (T1N0M0) esophageal cancer. PATIENTS AND METHODS: Between 1992 and 2003, 63 patients were enrolled in this study. Tumor depth was mucosal cancer (T1a) in 23 and submucosal cancer (T1b) in 40. CRT consisted of 55-66 Gy/50-60 fractions (median, 59.4 Gy); from 1 to 3 cycles (median, 2) of concurrent chemotherapy (Cisplatin and 5-fluorouracil), followed by high-dose-rate intraluminal brachytherapy 10-12 Gy/2-3 fractions. RESULTS: The 5-year overall and cause-specific and disease-free survival rates were 66.4%, 76.3%, and 63.7%, respectively. The 5-year cause-specific survival rates for T1a and T1b cancer patients were 85.2% and 70.0%, respectively (p = 0.06). The 5-year disease-free survival rates for T1a and T1b were 84.4% and 50.5%, respectively (p < 0.01). Esophageal fistula as a late toxicity occurred in 2 patients (G4: 1; G5: 1), and esophageal stricture requiring a liquid diet occurred in 2 patients. Pericardial effusion was observed in 3 patients. CONCLUSION: We confirmed that patients with T1N0M0 esophageal carcinoma had their esophagus preserved in 89.2% of cases after definitive CRT, and the survival rates were equivalent to those of previous reports of surgery.     

同步放化疗治疗局部晚期子宫颈鳞癌的临床研究

 目的 探讨同步放化疗治疗局部晚期子宫颈鳞癌的疗效及不良反应。方法 2001年至2002年收治121例60岁以下初治局部晚期子宫颈鳞癌患者，随机行同步放化疗（同步组）与单纯放疗（单放组）。所有患者均进行全盆野外照射4次／周， 2.0 Gy／次，量达30 Gy后，改为四野照射，放疗结束时B点剂量50 Gy；腔内治疗1次／周，A点剂量5 ~ 7 Gy／次，放疗结束时腔内治疗提供A点剂量40 ~ 45 Gy；同步组于腔内治疗前一天静脉滴注顺铂40 mg，1次／周，白细胞＜3.5×109／L时停止化疗。结果 同步组与单放组有效率分别为98.4 %、100 %，1、2、3年生存率分别为97.8 %和96.2 %、88.4 %和84.4 %、71.3 %和68.4 %，盆腔复发及远处转移率分别为21.0 %和16.9 %、11.3 %和15.3 %，差异均无统计学意义；恶心、呕吐以同步组程度略重、发生率高，差异有统计学意义。结论 同步放化疗较单纯放疗治疗60岁以下局部晚期子宫颈鳞癌，1、2、3年生存率未见显著提高，但生存质量有所改善，复发转移率未见改善，恶心、呕吐程度及发生率增高。     

External beam radiation therapy followed by high-dose-rate brachytherapy for inoperable superficial esophageal carcinoma

PURPOSE: The aim of this study was to retrospectively evaluate the feasibility, efficacy, and tolerance of external beam radiotherapy followed by high-dose-rate brachytherapy in inoperable patients with superficial esophageal cancer. PATIENTS AND METHODS: From November 1992 to May 1999, 66 patients with superficial esophageal cancer were treated with exclusive radiotherapy. The median age was 60 years (range, 41-85). Fifty-three percent of them were ineligible for surgery owing to synchronous or previously treated head-and-neck cancer. Most of the patients (n = 49) were evaluated with endoscopic ultrasonography (EUS) or computed tomography (CT). The mean doses of external beam radiotherapy and high-dose rate brachytherapy were 57.1 Gy (+/-4.83) and 8.82 Gy (+/-3.98), respectively. The most frequently used regimen was 60 Gy followed by 7 Gy at 5 mm depth in two applications. RESULTS: Among patients evaluated with EUS or CT, the complete response rate was 98%. The 3-, 5-, and 7-year survival rates were 57.9%, 35.6%, and 26.6%, respectively. Median overall survival was 3.8 years. The 5-year relapse-free survival and cause-specific survival were 54.6% and 76.9%. The 5-year overall, relapse-free, and cause-specific survival of the whole population of 66 patients was 33%, 53%, and 77%, respectively. Local failure occurred in 15 of 66 patients; 6 were treated with brachytherapy. Severe late toxicity (mostly esophageal stenosis) rated according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale occurred in 6 of 66 patients (9%). CONCLUSION: This well tolerated regimen may be a therapeutic alternative for inoperable patients with superficial esophageal cancer. Only a randomized study could be able to check the potential benefit of brachytherapy after external beam radiation in superficial esophageal cancer.     

食管癌患者同期放化疗顺铂加氟尿嘧啶方案Ⅱ期临床试验

背景与目的：国外已有研究表明,同期放化疗是局部晚期食管癌的标准治疗方案,但国内文献报道同期放化疗的疗效不尽相同,同期放化疗能否提高生存率尚无定论。本研究目的是评价PF方案同期放化疗对食管癌的疗效,并观察毒性。方法：44例食管鳞癌患者随机分为同期放化疗组（简称同期组）和后程加速超分割组（简称后超组）。同期组22例,全程常规分割照射,每天一次,每次2．0Gy,每周5次,25分割,总剂量50Gy。于放疗的第1天开始化疗：顺铂52．5mg／m^2 d1,氟尿嘧啶700mg／m^2 d1-d5,每28d重复,共4周期。后超组22例：总剂量60Gv,前半程30Gv同放化疗组,3周完成;后半程30Gv加速超分割照射,每日2次,间隔至少6h,每次1．5Gy,每周10次,2周完成。结果：同期组有效率高于后超组,分别为95．5％和86．4％,但差异无统计学意义（P=0．607）。同期组2年局控率和2年生存率分别为72．2％和56．7％,后超组分别为39．0％和31．6％。同期组获得了更高的局控率和生存率,但只有局控率差异有统计学意义（P=0．014）。两组的主要急性反应为放射性食管炎、放射性肺炎,晚期反应为食管和肺损伤。两组的急性和晚期反应均较轻。结论：同期放化疗与后程加速超分割相比,显著提高了食管癌局控率,有提高生存率的趋势,毒性可以耐受。     

放化疗中不同化疗方式对N3期鼻咽癌预后影响

目的 评价放化疗中不同方式化疗对N3期鼻咽癌患者预后的影响.方法 回顾分析114例N3期鼻咽癌患者资料.9例接受单纯放疗;105例接受以铂类为基础化疗联合放疗,其中同期放化疗37例,诱导化疗+同期放化疗53例,同期放化疗+辅助化疗15例.鼻咽原发灶采用60Co γ线、6 MV X线常规分割照射70 Gy,颈部根治量60～68 Gy,颈部预防量54～60 Gy.结果 中位随访时间54个月,共51例患者死亡.全组5年总生存率为59.1%.单纯放疗、同期放化疗、诱导化疗+同期放化疗、同期放化疗+辅助化疗的5年总生存率分别为17%、51%、68%、71%(X2=15.44,P=0.001),无复发生存率分别为83%、77%、88%、93%(X2=2.34,P:0.505),无转移生存率分别为17%、54%、72%、80%(X2=19.28,P=0.000).结论 诱导化疗+同期放化疗及同期放化疗+辅助化疗方式对N3期鼻咽癌患者比单纯同期放化疗更具优势,最有效治疗方式有待随机研究证实.

Abstract：

Objective Nasopharyngeal carcinoma patients with stage N3 disease are prone to develop distant metastasis even treated with standard concurrent chemoradiotherapy(CRT).The aim of this study is to compare the ettlcacy of difierent chemotherapy sequences in these patients.Methotis All patients with histologically proven,carcinoma of the nasopharynx treated between July 1999 and November 2003 were restaged according to the AJCC 2002 stage classification system.A total of 114 patients had AJCC N3 diseases were analyzed retrospectively.Patients were treated by conventional RT technique using 6 MV photons or 60 Coγ-ray with 1.8-2.0 Gy per fraction,5 fractions a week,to a planned dose of 70 Gy.The prophylactic irradiation dose of the neck wss 54-60 Gy.Any positive lymph node was boosted to a total dose of 60-68 Gy.All patients received cisplatin-based chemotherapy of difierent sequences but 9 patients RT alone.CRT regimen was delivered in 37 patients,neoadjuvant chemotherapy(NACT)+CRT regimen in 53 patients and CRT+adjuvant chemotherapy(AC)regimen in 15 patients.Results The prophylactic irradiation dose of the neck wss 54-60 Gy.Any positive lymph node was boosted to a total dose of 60-68 Gy.All patients received cisplatin-based chemotherapy of difierent sequences but 9 patients received RT alone.CRT regimen was delivered in 37 patients,neoadjuvant chemotherapy(NACT)+CRT regimen in 53 patients and CRT+adjuvant chemotherapy(AC)regimen in 15 patients.Results The median follow up time was 54 months(3-117months).The 5-year overall survival rate was 59.1%in whole groups,and with 17%,51%,68%and 71%in RT,CRT,NACT+CRT and CRT+AC group,respectively(X2=15.44,P=0.001).The 5-year relapse-free survival rates were 83%,77%,88%and 93%in RT,CRT,NACT+CRT and CRT+AC group,respectively(X2=2.34,P=0.505).The 5-year metastasis-free survival rates were 17%,54%,72%and 80%in RT,CRT,NACT+CRT and CRT+AC group,respectively(X2=19.28,P=0.000).Conclusions The NACT+CRT and CRT+AC regimens were more effective than CRT alone for N3 disease in the current study.Large prospective,randomized clinieal studies are warranted.     

同期放化疗治疗晚期口腔癌的临床观察

目的　探讨以顺铂为基础方案同期放化疗治疗中晚期口腔癌的疗效及急性毒性反应。方法　回顾分析４２例Ⅲ、ⅣＡ期或手术后复发的口腔鳞癌患者资料,分为放化疗组和单放组。放化疗组２２例患者行根治性外照射（４～８ＭＶＸ线,６０～７０Ｇｙ）,并于第１、４、８周行以顺铂（８０ｍｇ／ｍ^２）为基础的联合化疗;单放组２０例行单纯放疗（剂量同放化疗组）,观察比较两组近期疗效及急性毒性反应情况。结果　放化疗组和单放组有效率分别为８１。８％和６０。０％,１年生存率分别为４５。０％（９／２０）和２３。５％（４／１７）,２年生存率分别为２５。０％（４／１６）和７。７％（１／１３）,放化疗组的中位无局部进展生存期较单放组延长２个月。两组主要急性毒性反应为口腔黏膜炎、放射性皮炎、白细胞减少和恶心呕吐,放化疗组发生率均高于单放组,其中３～４级口腔黏膜炎两组差异显著（Ｐ＜０.０１）。结论　同期放化疗治疗晚期或手术后复发口腔癌的近期疗效优于单纯放疗,但主要不良反应中３～４级口腔黏膜炎较明显,需积极的对症及支持治疗。     

Combined chemo- and radiotherapy vs. radiotherapy alone in the treatment of primary, nonresectable adenocarcinoma of the rectum

PURPOSE: In a randomized study in primarily inextirpable rectal cancer, conventional radiotherapy to reduce the tumor mass was compared with combined chemotherapy and radiotherapy. METHODS AND MATERIALS: The combined treatment (CRT) was given every other week, four times, during a 7-week period. The drugs used were methotrexate, 5-fluorouracil in bolus injection followed by continuous infusion and leucovorin rescue. Radiotherapy (RT) was given simultaneously with five 2-Gy fractions in 3 days to a dose of 10 Gy to a total dose in the four courses of 40 Gy. This regimen was compared with radiotherapy in 2-Gy fractions to a total dose of 46 Gy in the radiotherapy group. Surgery was performed 3-4 weeks after finished treatment. Seventy patients were included between November 1988 and August 1996; 36 patients were allocated to RT and 34 to CRT. RESULTS: Twenty-five (74%) of the patients in the CRT group underwent a locally radical resection with 20 (59%) patients without any known metastases. The corresponding figures in the RT group were 23 (64%) and 18 (50%), respectively. Among the patients who underwent any tumor resection, 5/29 (17%) in the CRT group and 12/27 (44%, p = 0.05) in the RT group have had a local recurrence. After a locally radical resection, the corresponding figures are 4% and 35% (p = 0.02), respectively. Local disease-free survival was significantly superior in the CRT group (66% at 5 years) compared with the RT group (38%, p = 0.03 log-rank test). Five-year survival was 29% (9 patients) in the CRT group and 18% (6 patients) in the RT group, a nonsignificant difference (p = 0.3). Five patients in the RT group did not complete planned treatment, mainly due to the appearance of metastatic disease. In this group toxicity was usually of Grade 0-1. In the experimental group, the toxicity usually was Grade 2 or higher, and 6 patients did not manage to fulfill the planned treatment due to toxicity. CONCLUSION: In this study, with fewer included patients than intended, resectability rates were high in both groups. The addition of chemotherapy to radiotherapy significantly improved local control rates, but no statistically significant difference was found in survival between the groups. The acute toxicity after CRT was higher than after RT alone, but manageable.     

姑息性放疗与放化疗治疗伴有吞咽困难的Ⅳa/b期食管癌患者的疗效比较

目的:比较姑息性放疗与放化疗在伴有吞咽困难的食管鳞状细胞癌患者中的治疗效果。方法:我们纳入102例伴有吞咽困难的Ⅳa/b 期食管鳞癌患者,随机分为放疗（DT 50～60 Gy）或放化疗组（DT 50～60 Gy放疗联合5-氟尿嘧啶及顺铂化疗）,记录治疗前后吞咽困难评分及无营养支持生存时间。结果:放化疗组治疗后吞咽困难程度较放疗组治疗后吞咽困难程度轻,起初未接受营养支持的患者中,放疗组及放化疗组中位无营养支持生存时间分别为6.0个月及7.9个月（P=0.032）,中位生存时间分别为9.8个月及10.3个月（P=0.245）。放疗组白细胞减少发生率明显较放化疗组轻,其余不良反应发生率无统计学差异。结论:姑息性放疗及放化疗对于伴有吞咽困难的食管鳞癌患者均为有效的治疗手段,且放化疗效果更佳。     

Photodynamic therapy as salvage treatment for local failure after chemoradiotherapy in patients with esophageal squamous cell carcinoma: a phase II study

Local failure at the primary site is a major problem after chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC). Salvage surgery is the only treatment option with curative intent, but it is associated with high morbidity and mortality. The aim of this study was to evaluate the efficacy and safety of salvage photodynamic therapy (PDT) after CRT. Patients with histologically proven local failure limited to the submucosal layer, and without any metastasis after definitive CRT (≥50 Gy) for ESCC were enrolled in the study. PDT began with intravenous administration of 2 mg/kg of porfimer sodium followed 48-72 hr later by excimer dye laser irradiation with a fluence of 75 J/cm2. The primary endpoint was a complete response (CR) to treatment with PDT, and the secondary endpoints were toxicity related to PDT, progression-free survival (PFS) and overall survival (OS). Twenty-five patients were enrolled in the study. A CR was attained in 19 of 25 patients treated with PDT (CR rate, 76%; 95% CI, 55-91%). One treatment-related death (4%) caused by gastrointestinal hemorrhage at the irradiated site occurred 33 days after PDT. No adverse events greater than grade 3 were related to PDT in the other patients. After a median follow-up of 48 months after PDT, the PFS and OS at 3 years were 40% (95% CI, 21-59%) and 38% (95% CI, 17-60%), respectively. PDT is a potentially curative and tolerable salvage treatment after CRT for carefully selected patients with local failure without any metastasis.     

放疗联合方克顺铂同步或序贯化疗治疗老年晚期食管癌的临床研究

目的评价放疗联合方克顺铂同步或序贯化疗治疗老年食管癌的疗效及毒副反应。方法将62例〉70a的老年食管癌病人随机分成两组,同步放化疗组（31例）：放疗d1即同时开始化疗;序贯放化疗组31例：入组后先予化疗2个周期,再单独予放疗,放疗结束后再化疗2～3个周期,放疗采用6～Coy常规分割放疗,1．8～2．0Gy／次,5次／wk,总剂量64～68Gy／6～7wk完成。结果同步组和序贯组的有效率分别为93．6％、83．9％,1a、3a局部控制率分别为77．4％与67．7％和48．4％与38．7％,两组比较差异无统计学意义（χ^2=3．02,P=0．065）。同步组和序贯组的1a、3a生存率分别为74．2％与64．5％和45．1％与32.3％,两组比较差异无统计学意义（χ^2=2．32,P=0．073）。同步组的血液学毒性、放射性食管炎以及放射性肺炎均高于序贯组,多数为1以级。结论老年晚期食管癌病人同步治疗组较序贯治疗组的疗效提高,生存期延长,毒副作用增加,但病人可以耐受。     

HDR-brachytherapy boost for residual tumour after external beam radiotherapy in patients with tracheal malignancies.

Seven inoperable patients with tracheal neoplasms received a high dose rate (HDR) brachytherapy boost (median 15 Gy, single dose 3-5 Gy) for residual tumour after external beam radiotherapy (median 50 Gy, 5 x 2 Gy/week). The median actuarial survival was 34.3 months. The 1-, 2- and 3-year actuarial survival rates were 85.7%, 85.7% and 32%. Local control was obtained in 5/7 patients. Late toxicity occurred in three patients (stenosis n = 2, hemorrhage n = 1). Our data indicate, that a HDR brachytherapy boost is effective and feasible.     

A phase I/II study of external beam radiation, brachytherapy, and concurrent chemotherapy for patients with localized carcinoma of the esophagus (Radiation Therapy Oncology Group Study 9207): final report

BACKGROUND: A multiinstitutional, prospective study of the Radiation Therapy Oncology Group (RTOG) was designed to determine the feasibility and toxicity of chemotherapy, external beam radiation, and esophageal brachytherapy (EB) in a potentially curable group of patients with adenocarcinoma or squamous cell carcinoma of the esophagus. A preliminary analysis indicated a 17% 1-year actuarial risk of treatment-related fistulas. A final analysis of this study was considered important to determine the median survival time, local control, and late toxicity associated with this treatment regimen. METHODS: Planned treatment was 50 grays (Gy) of external beam radiation (25 fractions given over 5 weeks) followed 2 weeks later by EB (either high-dose-rate 5 Gy during Weeks 8, 9, and 10, for a total of 15 Gy, or low-dose-rate 20 Gy during Week 8). Chemotherapy was given during Weeks 1, 5, 8, and 11, with cisplatin 75 mg/m(2) and 5-fluorouracil 1000 mg/m(2)/24 hours in a 96-hour infusion. RESULTS: Of the 49 eligible patients, 45 (92%) had squamous histology and 4 (6%) had adenocarcinoma. Forty-seven patients (96%) completed external beam radiation plus at least 2 courses of chemotherapy, whereas 34 patients (69%) were able to complete external beam radiation, EB, and at least 2 courses of chemotherapy. The estimated survival rate at 12 months was 49%, with an estimated median survival of 11 months. Life-threatening toxicity or treatment-related death occurred in 12 (24%) and 5 (10%) cases, respectively. Treatment-related esophageal fistulas occurred in 6 cases (12% overall, 14% of patients starting EB) at 0.5-6.2 months from the first day of brachytherapy, leading to death in 3 cases. CONCLUSIONS: In this study, severe toxicity, including treatment-related fistulas, occurred within 7 months of brachytherapy. Based on the 12% incidence of fistulas, the authors continue to urge caution in employing EB, particularly when used in conjunction with chemotherapy.     

Neoadjuvant Concurrent Chemoradiotherapy Followed by Definitive High-Dose Radiotherapy or Surgery for Operable Thoracic Esophageal Carcinoma

Purpose: A prospective clinical trial was undertaken to investigate the feasibility of concurrent chemoradiotherapy for esophageal carcinomas.

Materials and Methods: Between June 1989 and May 1996, forty patients with operable squamous cell carcinoma of the thoracic esophagus (Stage 0 to III: UICC 1987), ages 45 to 78 years (mean: 64), were enrolled in a study of neoadjuvant concurrent chemoradiotherapy followed by definitive high-dose radiotherapy (CRT group) or surgery (CRT-S group). Neoadjuvant chemoradiotherapy consisted of 44 Gy in 40 fractions for 4 weeks (2.2 Gy/2 Fr/day) through 10-MVX rays, with 2 courses of cisplatin (80–100 mg/body, mean: 60 mg/m2, Day 1, bolus injection) and 5-fluorouracil (500–1000 mg/body/day, mean: 400 mg/m2, Days 1–4, continuous infusion). After completion of neoadjuvant chemoradiotherapy, an intermediate clinical response was assessed by barium swallow, esophagoscopy with/without biopsy, EUS in most cases, thoracic and upper abdominal CT scan, and cervical US. Definitive chemoradiotherapy was performed in patients when regression of more than 75% was evident (CRT Group), and esophageal resection was indicated in those who remained at less than 75% (CRT-S Group). In CRT Group, a cumulative dose of 60–70 Gy for Tis, T1 and 65–75 Gy for T2–T4 tumor with high-dose–rate intraluminal brachytherapy and a total of 3 courses of chemotherapy were planned. In CRT-S Group, intraoperative radiotherapy for abdominal lymphatic system and postoperative supraclavicular irradiation were added.

Results: At the time of intermediate assessment, complete response (CR) was observed in 16 patients, a partial response (PR) in 22, and no change (NC) in 2. Thirty responding patients (CR, 16; PR, 14) entered the CRT Group, and 10 nonresponding patients (PR, 8; NC, 2) were followed by surgery (CRT-S Group). Radiotherapy was completed satisfactorily, but chemotherapy was suspended in 26 patients (65%) because of acute toxicity. Clinical CR rate at the completion of treatment showed 90% in CRT Group, and pathologic CR rate 10% in CRT-S Group. The overall median survival was 45 months, survival at 1, 2, and 3 years being 100%, 72%, and 56%, respectively. Local-regional failure was observed in 7 patients (all in CRT Group), distant failure in 6 (3 in CRT Group, 3 in CRT-S Group) and local-regional with distant failure in 1 (CRT Group). Four patients with local-regional recurrence in the CRT Group were salvaged by surgery. Overall survival at 2 and 3 years for CRT vs. CRT-S Group was 72%, 64% vs. 75%, 38%, respectively. No treatment-related mortality was observed. The rate of the ’esophagus conservation’ was 65% (Stage 0: 1 of 1, 100%; Stage I: 11 of 12, 92%; Stage II: 8 of 17, 47%; Stage III: 6 of 10, 60%).

Conclusion: Our results demonstrated that almost all early disease (Stage 0–I) and about half of advanced disease (Stage II–III) could be conserved, their esophagus treated by the multidisciplinary approach centering on high-dose radiotherapy and concurrent chemotherapy.