Fast neutron teletherapy for advanced carcinomas of the oropharynx.

A study was performed to assess the efficacy of using fast neutron irradiation to treat advanced squamous cell carcinomas of the oropharynx. Twenty-seven patients were treated with neutrons alone and 21 patients received a combination of fast neutrons and megavoltage photons as part of a mixed beam fractionation scheme. All patients in the study were judged to have less than a 10% chance for 5-year survival with conventional therapy.In the neutron-only group, the initial complete remission rate was 44% (12/27) and the duration of local control ranged between 2–41 months (mean = 12.4 months). At the time of writing, 2 patients in this group were still alive and free of disease while 5 patients had died without evidence of tumor at the primary site. The other 15 patients achieved only a partial remission and after completing therapy, their survival ranged between 1 and 15.5 months (mean = 3.2 months).In the mixed beam group, the initial complete remission rate was 67% (14/21) and the duration of local control ranged between 4 and 44 months (mean = 18 months). At the time of writing, 5 patients in this group were still alive and free of disease at the primary site. An additional 3 patients were salvaged successfully with surgery after either an initial control failure or a recurrence. Three other patients died free of disease at the primary site. The survival of the 6 patients in whom there was no initial local control or surgical salvage ranged between 0.5 and 8.5 months (mean = 4.0 months) after completing therapy.Actuarially calculated curves for the duration of local control are shown for the 2 groups of patients and at all follow-up times, the mixed beam group shows a higher degree of local control at the primary site than the neutron-only group. However, because of the small number of patients at risk for the longer follow-up times, this difference is statistically significant only for the initial rate of local control. Assuming an RBE = 3 for the neutron radiation, in all cases the spinal cord dosage was limited to 4500 photon rad equivalent. In the neutron-only group, 10 patients survived 10 months or longer and of these, 5 developed an apparent cervical myelitis. No such complications were noted in the mixed beam group and so it appears that the RBE is greater than 3 for late damage to the spinal cord. In the context of this study, it appears that mixed beam (neutron/photon) irradiation is superior to neutrons alone, both in terms of local control and long-term morbidity, for treating advanced tumors of the oropharynx.     

Three-dimensional conformal radiation therapy for squamous cell carcinoma of the esophagus: A prospective phase I/II study

Purpose

A prospective phase I-II study was conducted to determine the tolerance and local control rate of three-dimensional conformal radiotherapy (3-DCRT) for esophageal squamous cell carcinoma (SCC).

Methods and materials

Thirty patients underwent 3-DCRT for thoracic esophageal SCC. PTV1 composed of a 1.2-1.5 cm margin lateral around GTV and 3.0 cm margin superior/inferior of GTV. PTV2 encompassed GTV with a margin of 0.5-0.7 cm. The dose for PTV1 was 50 Gy in 2 Gy daily fractions; PTV2 received a boost of 16 Gy in 2 Gy daily fractions to a total dose of 66 Gy.

Results

Median follow-up time was 18 months. The most common acute toxicity was esophagitis in 63% of patients with RTOG grades 1-2, and in 3% with grade 3. RTOG grades 1-2 radiation pneumonitis developed in 27% of patients. One patient developed pulmonary fibrosis RTOG grade 2 and another patient experienced grade 3 pulmonary fibrosis. Two patients developed mild esophageal stricture requiring dilatation. Two-year overall survival, local disease progression-free rate, and distant metastasis-free rate were 69%, 36% and 56%, respectively.

Conclusions

Although 3-DCRT to 66 Gy for esophageal SCC was well tolerated, the local control was disappointing. The result supports the use of chemoradiation as the standard care for esophageal SCC.     

Radiation Therapy Oncology Group Phase I-II study on fast neutron teletherapy for carcinoma of the bladder

From June 1977 through March 1981, the Radiation Therapy Oncology Group sponsored a Phase I-II study (RTOG 77-05) on the use of fast neutrons for treating carcinomas of the urinary bladder. Patients entered on the study had Stage B1 (grade III or IV histology) or Stage B2, C, or D1 (any grade histology) disease. Thirteen patients received preoperative mixed-beam (neutron/photon) irradiation to 50 photon Gy-equivalent, and in 12 of these a cystectomy was performed in 4 to 6 weeks. The incidence of pathologic downstaging to Po was 58% in the cystectomy specimens. The projected survival at 30 months is 32%. Twenty-six patients were treated definitively with mixed-beam irradiation consisting of 50 photon Gy-equivalent to the pelvis followed by a 20 photon Gy-equivalent boost to the bladder itself. Eighteen of 26 patients (69%) achieved tumor clearance at some time during their follow-up but 8/18 (44%) of these ultimately exhibited some component of local failure. The projected survival at 30 months for this group of patients is 34%. However, the subset of patients with Stage B or C disease had a projected survival at 30 months of 60%. Four patients received definitive neutron irradiation alone and 3/4 achieved tumor clearance at some time during their follow-up. Actuarial curves are presented for patient survival and duration of local control, and results are compared with comparably staged patients treated with megavoltage photon irradiation. Treatment-related morbidity is also discussed.     

食管癌后程加速超分割放疗同期化疗的Ⅲ期临床研究

目的观察食管癌单纯后程加速超分割放疗和后程加速超分割放疗加PF方案同期化疗的副反应,分析治疗失败原因和生存情况。方法111例食管鳞癌随机分成单纯后程加速超分割放疗组(放疗组)57例,后程加速超分割放疗加PF方案同期化疗组(放化疗组)54例。放疗组前2/3疗程放疗用常规分割放疗,后1/3疗程缩野加速超分割放疗,总剂量68．4 Gy(41分次,42～44d完成)。放化疗组放疗方案同单纯放疗组,化疗在放疗的第1天开始,顺铂25mg/(m~2·d)3 d,氟尿嘧啶600mg/ (m~2·d)3d,4周为1个疗程,共4个疗程。结果中位随访时间67．1个月(47．6～76．4个月)。放化疗组1、3、5年生存率分别为67%、44%和40%,放疗组分别为77%、39%和28%(P=0．310)。放化疗组3+4级急性毒副反应为42%,放疗组为25%(P＜0．05)。放化疗组有3例患者在治疗过程中死亡。结论后程加速超分割放疗加PF方案同期化疗食管癌比单纯后程加速超分割放疗有提高生存率的趋势,但急性毒副反应明显增加,最终结论需大样本的研究结果。     

食管基底细胞样鳞癌的诊断与治疗

目的 观察食管基底细胞样鳞癌的临床和病理组织学特征,探讨其诊断、鉴别诊断及治疗方法.方法 对23例食管基底细胞样鳞癌患者的临床和病理资料进行回顾性分析.结果 食管基底细胞样鳞癌发病年龄较大,临床表现和影像学特点与鳞癌相似,以溃疡型多见;治疗首选手术,术后应结合放化疗.本组23例食管基底细胞样鳞癌患者的1、2和3年生存率分别为60.9%、21.7%和0.结论 食管基底细胞样鳞癌具有恶性程度高、进展快、转移早和预后差等特点,临床上应采用根治性手术并结合术后放化疗的治疗方案.     

细胞周期调节蛋白在食管鳞癌组织中的表达

背景与目的:研究表明肿瘤细胞周期分析显示细胞具高增殖率的肿瘤,其临床病情发展快;细胞周期调节蛋白Ki-67、细胞周期蛋白A及p27介入到细胞的增殖,但这些因子与食管癌之间的关系的研究在我国尚未见报道。本研究观察细胞周期调节蛋白Ki-67、细胞周期蛋白A及p27在中国食管癌患者中的表达特征,以探讨这些分子标志物与临床病理因素之间的关系。方法:60例(48例男性、12例女性)食管鳞癌患者行外科手术切除肿瘤,其标本行免疫组织化学染色。Ki-67及细胞周期蛋白A表达程度以染色指数表示,p27以标记指数表示。结果:Ki-67、细胞周期蛋白A及p27免疫组化染色在瘤组织与非瘤组织中均固定于细胞核。Ki-67及细胞周期蛋白A的染色指数在低分化鳞癌(27.2±4.9;15.4±5.3)明显高于高分化鳞癌(20.6±6.3;11.3±6.4,P<0.05);p27免疫组化染色的阳性率在高分化鳞癌(36%)高于其它病理类型(29%及18%),但相互之间的差异无统计学意义(P>0.05)。结论:Ki-67、细胞周期蛋白A及p27的表达程度可反映食管鳞癌细胞的增殖状况。细胞周期调节蛋白Ki-67及细胞周期蛋白A的过度表达提示食管鳞癌细胞分化差。     

Phase II evaluation of combined cisplatin and vindesine in advanced squamous cell carcinoma of the esophagus: Japanese Esophageal Oncology Group Trial

In the present phase II study, 31 patients with advanced measurable esophageal carcinomas were treated with a combination of 30 mg vindesine/m2 and 70 mg cisplatin/m2. The overall response rate was 16.1% (95% confidence limits, 7.1-32.6%). Responses were seen in metastatic sites, including the liver in two patients, a lung in one, neck or mediastinal lymph nodes in two and primary sites in two. The response durations were between one and two months for patients achieving partial response. The average survival time after first administration was 5.5 months for patients who responded to treatment, whereas, for those who did not, it was 7.3 months. The major form of toxicity was myelosuppression, 14 patients developed grade 2-3 toxicity and one sepsis which led to death. No superiority of the combined chemotherapy over either cisplatin or vindesine therapy alone was suggested for cases of advanced squamous cell carcinoma of the esophagus by the present study.     

食管鳞癌西妥昔单抗联合同期放化疗的初步临床研究

目的 观察西妥昔单抗联合同期放化疗对食管鳞癌的安全性及近期疗效 方法 19例 Ⅰ~Ⅲ 期无远处转移的食管鳞癌患者入组,西妥昔单抗静脉滴注1 次/周, 第1周为400 mg/m²,第2~8周为250 mg/m², 每周联合紫杉醇45 mg/m²和顺铂20 mg/m²。第2~8周调强放疗59.4 Gy分33次。结果 2例 患者因严重不良反应出组, 17例的有效率为100%,其中完全缓解率为71%(12例)。中位随访时间29.3个月, 1年 总生存率、无复发生存率分别为100%,82%。19例 患者主要不良反应为骨髓抑制、黏膜反应、皮疹等,其中≥2级粒细胞减少、放射性食管炎、皮疹发生率分别为89%、84%、58%。2例局部复发, 1例后颈部淋巴结及肺转移。结论 西妥昔单抗联合同期放化疗对食管鳞癌安全有效,值得扩大样本量进行进一步临床研究。     

Salvage surgery after failed chemoradiotherapy in squamous cell carcinoma of the esophagus

Aims

To investigate the survival benefit and preoperative risk factors for hospital mortality of salvage surgery in esophageal cancer patients who had locoregional residual/recurrent tumor after definitive chemoradiotherapy.

Methods

We retrospectively reviewed the esophageal cancer patients who presented at our hospital from 1997 to 2004. Forty-seven patients who had squamous cell cancer and developed locoregional recurrent/persistent disease after primary definitive chemoradiotherapy were elected. Twenty-seven of them received salvage esophagectomy (group 1) and the other 20 underwent non-operative treatment only (group 2). In order to assess the surgery-related mobility and mortality in group 1, 191 patients who received neoadjuvant chemoradiotherapy followed by operation during the same time period were also enrolled (group 3).

Results

The 5-year overall survival of group 1 patients was 25.4%. In contrast, all of the patients in the group 2 died within 16.7 months. The difference was statistically significant (p = 0.0029). In comparison with group 3, group 1 patients had significantly more surgery-related complications and hospital mortality. In univariate analysis for preoperative risk factors, a low albumin or hemoglobulin level was associated with high hospital mortality in group 1 (p = 0.004 and 0.003, respectively). After multivariate analysis, only the low albumin level remained borderline significance. As for disease specific survival after salvage surgery, R0 resection was the only independent prognosticator (p = 0.049).

Conclusion

Salvage surgery provides survival benefit in esophageal cancer patients with locoregional persistent or recurrent disease after primary definitive chemoradiotherapy. Preoperative albumin and hemoglobulin levels are associated with hospital mortality and may aid in selecting suitable patient for salvage surgery.     

胸段食管鳞癌切除术后的预后分析

目的：应用Ｃｏｘ模型和Ｋａｐｌａｎ－Ｍｅｉｅｒ生存分析方法,对可能影响食管鳞癌术后生存时间的临床和病理因素的相关性进行了分析。方法：我科１９９１年８月～１９９６年３月行胸段食管癌切除术并经病理证实为原发性食管鳞癌的患者共１３６例,排除手术死亡４例,有完整随访资料的１１５例,结合临床和病理情况及预后相关资料,选择性别、年龄、肿瘤部位等１４个有关食管鳞癌术后生存的非重复特征性因素进行分层,应用ＳＴＡＴ     

Neoadjuvant treatment for esophageal squamous cell carcinoma

Squamous cell carcinoma and adenocarcinoma are types of esophageal cancer, one of the most aggressive malignant diseases. Since both histological types present entirely different diseases with different epidemiology, pathogenesis and tumor biology, separate therapeutic strategies should be developed against each type. While surgical resection remains the dominant therapeutic intervention for patients with operable esophageal squamous cell carcinoma (ESCC), alternative strategies are actively sought to reduce the frequency of post-operative local or distant disease recurrence. Such strategies are particularly sought in the preoperative setting. Currently, the optimal management of resectable ESCC differs widely between Western and Asian countries (such as Japan). While Western countries focus on neoadjuvant or definitive chemoradiotherapy, neoadjuvant chemotherapy followed by surgery is the standard treatment in Japan. Importantly, each country and region has established its own therapeutic strategy from the results of local randomized control trials. This review discusses the current knowledge, available data and information regarding neoadjuvant treatment for operable ESCC.     

基质金属蛋白酶16在食管鳞癌中的表达及其生物学功能

背景与目的：中国是世界上食管癌的高发区,食管癌可发生早期淋巴结及血行转移,这使其表现出临床进展迅速并且预后很差的特性。研究显示癌组织侵袭和转移与其诱导产生的蛋白酶降解细胞外基质、基底膜能力密切相关,因此基质金属蛋白酶(matrix metalloproteinase,MMP)在肿瘤的发生、发展、转移过程中发挥重要作用,本文研究基质金属蛋白酶16(matrix metalloproteinase-16,MMP-16)在食管癌中的表达及其与食管癌浸润转移的关系,并为食管癌早期诊断及靶向治疗提供理论依据。方法：应用免疫组化、蛋白质印迹法(Western blot)及实时定量聚合酶链反应(real-time polymerase chain reaction,RTPCR)检测食管癌及相应的正常组织的MMP-16蛋白表达水平和MMP-16 mRNA转录情况,并对其临床意义进行探讨。通过构建针对MMP-16的小片段发夹状RNA(shRNA)干扰表达质粒,应用划痕实验、Transwell小室实验、WST-1及流式细胞仪检测方法,研究shRNA表达质粒沉默MMP-16后对Eca109细胞的迁移、侵袭、增殖及凋亡水平的影响。采用t检验进行统计学分析。结果：在蛋白水平,MMP-16在癌组织和正常组织表达平均指数分别为0.569±0.380和1.483±0.982,差异有统计学意义(P<0.01)。MMP-16表达与食管鳞癌组织分化程度呈正相关(R=0.704,P<0.05),与肿瘤的分期负相关(P<0.05)。干扰MMP-16的表达后Ec109细胞侵袭及迁移能力明显增加(P<0.05),细胞凋亡水平下降,增殖差异无统计学意义(P>0.05)。结论：MMP-16在食管癌组织中低表达,随着细胞分化程度增加而表达增加,在Eca109细胞中干扰MMP-16后能够抑制肿瘤细胞的迁移、侵袭,并减少凋亡水平,MMP-16在食管癌中可能起保护作用。     

Phase II evaluation of cisplatin and 5-fluorouracil in advanced squamous cell carcinoma of the esophagus: a Japanese Esophageal Oncology Group Trial.

Thirty-nine patients with advanced measurable squamous cell carcinomas were treated with two or more courses of 70 mg cisplatin/m2 on day 1 and 700 mg infused 5-fluorouracil/m2 on days 1-5 every 21 days. The overall response rate was 35.9 (95% confidence limits, 24.8-55.1%). Responses were seen in primary sites in the esophagus of five patients, in the lung of seven, the liver of one and the mediastinal lymph nodes of one. The average response duration was 3.5 (range 1-12) mo for patients who achieved partial response. The average survival time after the first administration was 9.5 mo for patients who responded to the treatment whereas, for those who did not, it was 5.6 mo. The major form of toxicity was myelosuppression and there were six patients with grade 3 toxicity and one with grade 4. The present study was designed to evaluate the effectiveness of combined cisplatin and 5-fluorouracil for advanced squamous cell carcinoma, and the results showed that it had a reasonable effect and might possibly be used as a postoperative chemotherapy because of its mild side effects.     

Phase II study of aminothiadiazole in advanced squamous cell carcinoma of the esophagus

Twenty-three patients with advanced inoperable squamous cell carcinoma of the esophagus were treated with aminothiadiazole (A-TD) 125 mg/m2 weekly plus allopurinol daily in a phase II cooperative group trial. No patients responded to treatment; 17 patients progressed, three showed stable disease, and three were unevaluable. There were no life-threatening hematologic or metabolic toxicities. The median survival from study entry was 5 months. A-TD is not active in advanced squamous cell carcinoma of the esophagus.     

Preoperative radiation and chemotherapy for localized squamous cell carcinoma of the esophagus: a RTOG Study

Forty-one evaluable patients with localized squamous cell carcinoma of the thoracic esophagus were treated by a course of radiation therapy (3000 cGy in 3 weeks), 5-Fluorouracil (5-FU) and Cis-platinum (Pt). This was followed by an esophagectomy in medically eligible patients who agreed to the procedure and who had no evidence of extrathoracic tumor. If tumor was found in the specimen, an added 2000 cGy of radiation therapy and additional 5-FU and Pt were given. One-year survival was 44%, 2-year survival 15%, and 3-year survival 8%. All 3-year survivors had tumor-free specimens, but one patient with tumor in the thorax and subdiaphragmatic metastasis survived 2 years.     

ACHALASIA AND CARCINOMA OF THE ESOPHAGUS

ＡＣＨＡＬＡＳＩＡＡＮＤＣＡＲＣＩＮＯＭＡＯＦＴＨＥＥＳＯＰＨＡＧＵＳＥｕｇｅｎｉｏＦｉｏｒｅｎｔｉｎｏ；ＷｕＨｕａｉｓｈｅｎ；吴怀申；ＡｌｆｏｎｓｏＭＭａｉｏｒａｎａ；ＣｈｅｎＷｅｎｈｕ；陈文虎；ＺｈｏｕＹｕｎｚｈｏｎｇ；周允中（Ｉｎｓｔｉｔｕｔｅ...     

Elective nodal irradiation (ENI) in definitive chemoradiotherapy (CRT) for squamous cell carcinoma of the thoracic esophagus

Background and purpose

There are some reports indicating that prophylactic three-field lymph node dissection for esophageal cancer can lead to improved survival. But the benefit of ENI in CRT for thoracic esophageal cancer remains controversial. The purpose of the present study is to retrospectively evaluate the efficacy of elective nodal irradiation (ENI) in definitive chemoradiotherapy (CRT) for thoracic esophageal cancer.

Materials and methods

Patients with squamous cell carcinoma (SCC) of the thoracic esophagus newly diagnosed between February 1999 and April 2001 in our institution was recruited from our database. Definitive chemoradiotherapy consisted of two cycles of cisplatin/5FU repeated every 5 weeks, with concurrent radiation therapy of 60 Gy in 30 fractions. Up to 40 Gy radiation therapy was delivered to the cervical, periesophageal, mediastinal and perigastric lymph nodes as ENI.

Results

One hundred two patients were included in this analysis, and their characteristics were as follows: median age, 65 years; male/female, 85/17; T1/T2/T3/T4, 16/11/61/14; N0/N1, 48/54; M0/M1, 84/18. The median follow-up period for the surviving patients was 41 months. Sixty patients achieved complete response (CR). After achieving CR, only one (1.0%; 95% CI, 0-5.3%) patient experienced elective nodal failure without any other site of recurrence.

Conclusion

In CRT for esophageal SCC, ENI is effective for preventing regional nodal failure. Further evaluation of whether ENI leads to an improved overall survival is needed.     

食管鳞癌三维适形放疗同步化疗的临床研究

 【摘 要】 目的　观察三维适形放疗（3D-CRT）同步化疗对食管鳞状细胞癌的疗效及不良反应。方法 67例食管鳞状细胞癌患者分为同步放化疗组（观察组）35例、单纯放疗组（对照组）32例,两组均采用3D-CRT,处方剂量2Gy/次,5次/周,总剂量60~66 Gy/30~33次;观察组采用PF方案化疗,28 d为1周期,共2周期,化疗的第1d同步放疗,放疗结束后,再进行2~4周期化疗。结果　观察组、对照组有效率分别为85.7%（30/35）和62.5%（20/32）,1、2、3年生存率分别为82.6%和62.2%、44.4%和69.7%、53.9%和25.0%,中位生存时间分别为33.0和27.0个月,差异有统计学意义（均P＜0.05）。急性不良反应主要为放射性食管炎、骨髓抑制、恶心、呕吐。结论 3D-CRT同步化疗治疗食管鳞状细胞癌可取得较好的疗效,不良反应可耐受,有较高的临床可行性。     

紫杉醇联合顺铂治疗晚期食管鳞癌

目的研究紫杉醇联合顺铂治疗晚期食管癌的疗效和毒副反应。方法30例晚期食管磷癌患者中,27例为初次化疗患者,3例患者曾接受术后辅助化疗。中位年龄58岁。紫杉醇175mg／m^2,d1,静脉滴注3h;顺铂40mg/m^2,d2,d3;21d为1个周期。结果30例患者共完成89个化疗周期。在可评价疗效的27例患者中,完全缓解5例(18．5％),部分缓解11例(40．7％),有效率为59．3％。中位疾病进展时间为5．0个月,中位生存时间9．7个月。可评价毒副反应28例,其主要的毒副反应为脱发,有5例(17．9％)患者出现Ⅲ-Ⅳ度中性粒细胞降低。结论紫杉醇联合顺铂对晚期食管癌疗效肯定,可以考虑作为治疗晚期食管癌的主要治疗方案。