A randomized clinical trial of radiation therapy versus thermoradiotherapy in stage IIIB cervical carcinoma

To clarify the role of thermoradiotherapy for FIGO Stage IIIB cervical carcinomas, both the clinical response and survival of patients treated with radio- or thermoradiotherapy were investigated. Forty patients with Stage IIIB uterine cervix carcinoma were treated with external beam irradiation to the pelvis, combined with iridium 192 high-dose-rate intracavitary brachytherapy. All patients were divided randomly into the following two groups: the radiotherapy (RT) group of 20 patients, who underwent radiotherapy alone; and the thermoradiotherapy (TRT) group of 20 patients, who underwent three sessions of hyperthermia in addition to radiotherapy. The primary endpoint of this study was local complete response and survival. A complete response was achieved in 50% (10 of 20) in the RT group versus 80% (16 of 20) in the TRT group (p = 0.048). The 3-year overall survival and disease-free survival of the patients who were treated with TRT (58.2 and 63.6%) were better than those of the patients treated with RT (48.1 and 45%), but these differences were not significant. The 3-year local relapse-free survival of the patients who were treated with TRT (79.7%) was significantly better than that of the patients treated with RT (48.5%) (p = 0.048). TRT, as delivered in this trial, was well tolerated and did not significantly add to either the relevant clinical acute or long-term toxicity over radiation alone. TRT resulted in a better treatment response and 3-year local relapse-free survival rate than RT for patients with FIGO Stage IIIB cervical carcinoma.     

A randomized clinical trial of radiation therapy versus thermoradiotherapy in stage IIIB cervical carcinoma.

To clarify the role of thermoradiotherapy for FIGO Stage IIIB cervical carcinomas, both the clinical response and survival of patients treated with radio- or thermoradiotherapy were investigated. Forty patients with Stage IIIB uterine cervix carcinoma were treated with external beam irradiation to the pelvis, combined with iridium 192 high-dose-rate intracavitary brachytherapy. All patients were divided randomly into the following two groups: the radiotherapy (RT) group of 20 patients, who underwent radiotherapy alone; and the thermoradiotherapy (TRT) group of 20 patients, who underwent three sessions of hyperthermia in addition to radiotherapy. The primary endpoint of this study was local complete response and survival. A complete response was achieved in 50% (10 of 20) in the RT group versus 80% (16 of 20) in the TRT group (p = 0.048). The 3-year overall survival and disease-free survival of the patients who were treated with TRT (58.2 and 63.6%) were better than those of the patients treated with RT (48.1 and 45%), but these differences were not significant. The 3-year local relapse-free survival of the patients who were treated with TRT (79.7%) was significantly better than that of the patients treated with RT (48.5%) (p = 0.048). TRT, as delivered in this trial, was well tolerated and did not significantly add to either the relevant clinical acute or long-term toxicity over radiation alone. TRT resulted in a better treatment response and 3-year local relapse-free survival rate than RT for patients with FIGO Stage IIIB cervical carcinoma.     

Bax and Bcl-2 protein expression following radiation therapy versus radiation plus thermoradiotherapy in stage IIIB cervical carcinoma

BACKGROUND: The relative amounts of Bcl-2 and Bax proteins determine cell survival or death following an apoptotic stimulus. To clarify the molecular mechanism of cell death after radiotherapy or thermoradiotherapy and its relation to the response of AJCC/UICC Stage IIIB cervical carcinomas, the expression of Bax and Bcl-2 proteins was investigated both before and in the course of treatment given during this study. METHODS: Thirty-seven patients with Stage IIIB carcinoma of the uterine cervix were treated with external beam irradiation to the pelvis combined with iridium-192 high-dose-rate intracavitary brachytherapy. All patients were randomized to one of the following two groups: the radiotherapy (RT) group of 19 patients who were given radiotherapy alone, and the thermoradiotherapy (TRT) group of 18 patients who were given 3 sessions of hyperthermia in addition to RT. Specimens of the cervical tumors were obtained by punch biopsy both before and in the course of the treatment (after a total dose of 10.8 grays ?Gy for the RT group or after 10.8 Gy plus 1 session of hyperthermia for the TRT group). The tumor sections were stained with anti-Bax and anti-Bcl-2 monoclonal antibody. On the basis of the percentage of immunopositive cells, both pretreatment and posttreatment samples were scored. Furthermore, relative changes in protein expression were determined by comparing the pretreatment scores with those in the course of treatment. In addition, treatment response was evaluated. RESULTS: A complete response was achieved in 52.6% (10 of 19) of the RT group versus 83. 3% (15 of 18) of the TRT group (P = 0.049). Better tumor control was accompanied by increased Bax expression, i.e., 10.5% (2 of 19) of the RT group versus 44.4% (8 of 18) of the TRT group (P = 0.02). The respective number of patients who partially responded (PR) or did not respond to treatment (NC) was 26.3% (5 of 19) and 21.1% (4 of 19) of the RT group versus 11.1% (2 of 18) and 5.6% (1 of 18) of the TRT group (P = 0.2 for both the PR and NC subgroups). CONCLUSIONS: TRT was found to result in better treatment responses than RT for patients with Stage IIIB cervical carcinoma. An additive or synergistic antitumor effect of TRT is likely to occur through induction of apoptosis involving one of the bax pathways.     

Randomized phase II study of immunomodulator Z-100 in patients with stage IIIB cervical cancer with radiation therapy

OBJECTIVE: To find the optimal dose of immunomodulator Z-100 in patients with stage IIIB squamous cell carcinoma of the cervix in combination with radiation therapy. METHODS: The patients were randomly assigned to the dosage levels of 2, 20 or 40 mug of Z-100. Z-100 was subcutaneously injected twice a week during radiotherapy and once in two weeks during the maintenance period. The response rate after radiotherapy was evaluated, and the optimal clinical dosage was then determined. Safety of Z-100 was evaluated during the radiation therapy and maintenance therapy. Survival was also evaluated. RESULTS: A total of 116 patients were entered. The adverse reactions were not dose-dependent and no serious toxicities were observed. The response rates were 72.2% (26/36) in the 2 microg group, 84.6% (33/39) in the 20 microg group and 94.3% (33/35) in the 40 microg group (P = 0.006). However, the survival was not significantly different. CONCLUSIONS: The optimal dose of Z-100 was determined to be 40 mug in combination with radiation therapy for stage IIIB cervical cancer. However, impact of Z-100 on survival must be determined by the placebo controlled randomized trial, because survival benefit was not observed in this small population study.     

Ⅰb～Ⅱb期宫颈癌术前辅助化疗、放疗的疗效分析

目的 :探讨术前新辅助化疗、放疗对Ⅰb～Ⅱb期宫颈癌高危患者的疗效。方法 :选择Ⅰb～Ⅱb期宫颈癌高危患者 (巨块型、分化差、未分化或腺癌 ) ,分术前化疗组、术前放疗组、以及同期治疗直接行根治性子宫切除加盆淋清扫术为对照组。结果 :①新辅助化疗组 4 0例 ,盆腔淋巴转移 2例 ,与单手术组 (46 / 2 30 )比较盆腔淋巴转移显著减少 (P <0 .0 2 )。化疗敏感者 (33/ 4 0 )的盆腔淋巴转移危险降低 (P =0 .0 2 7)。②术前腔内放疗 16例可以缩小肿瘤病灶但对盆腔淋巴转移作用不大 (P >0 .0 5 )。结论 :术前化疗对Ⅰb～Ⅱb期宫颈癌高危患者有效 ,可以提高手术切除率 ,消除淋巴结转移和亚临床病灶 ,改善长期存活 ,减少术后辅助放疗机率 ,为提高生存质量带来益处。化疗不敏感者可能预后不良。术前腔内放疗可提高手术切除率 ,但对预后可能影响不大。     

A randomized trial of chemotherapy followed by pelvic radiation therapy in stage IIIB carcinoma of the cervix.

Because of the poor results in stage III B carcinoma of the cervix with standard treatment using radiotherapy alone, we designed a randomized trial to determine whether administration of chemotherapy before pelvic irradiation would improve survival. Between May 1984 and August 1986, 107 patients with previously untreated squamous cell carcinoma were randomly assigned, after stratification by age (less than 50 v greater than 50 years), extent of parametrial involvement (unilateral v bilateral), and lymphangiographic findings (negative v positive) to pelvic radiotherapy (RT; arm A) or three cycles of chemotherapy (CT; bleomycin, vincristine, mitomycin, and cisplatin [BOMP]), followed by the same radiotherapy regimen (CT + RT; arm B). The groups were balanced by age, performance status, extent of parametrial involvement, bulkiness of cervical disease, nodal involvement, and presence of hydronephrosis. Minimal follow-up is 34 months. A complete local response was observed in 32.5% of the patients in arm A and in 47% of the patients in arm B (P = .19). Overall 5-year survival rates were 39% for the RT arm and 23% for the CT + RT approach (P = .02). Toxicity was severe in arm B and included fatal pulmonary toxicity in four patients. Locoregional and distant failures were similar in both groups. We conclude that, despite a satisfactory response rate, neoadjuvant BOMP chemotherapy adversely affects survival in stage III B cervical cancer and is associated with unacceptable toxicity.     

Hydroxyurea plus pelvic radiation versus placebo plus pelvic radiation in surgically staged stage IIIB cervical cancer

Forty-five evaluable patients with stage IIIB carcinoma of the uterine cervix were entered into a prospective, double-blind, randomized study to evaluate the possible radiation-potentiating properties of hydroxyurea. All patients were documented to be without para-aortic lymph node metastasis by pretherapy staging para-aortic lymphadenectomy. The original plan of therapy was for continuous therapy (200 rads/day) of 6,000 rads of pelvic radiation for 6 weeks plus intrauterine radium. However, 16 patients received 6,000 rads in 8 weeks by split-course therapy (2-week rest after 3,000 rads) plus radium. Twenty-nine patients received the planned continuous therapy. The median dose of pelvic radiation for patients who received continuous therapy or split-course radiation was 6,000 rads. Leukopenia (WBC less than 2,500/mm3) was significantly increased in the patients given hydroxyurea as compared to those given placebo (P less than .001). There was no statistically significant difference relative to anemia, thrombocytopenia, radiation skin reaction, diarrhea, or radiation-induced complications requiring surgical correction. The estimated 5-year progression-free survival rate for the combined, continuous, and split-course radiation therapy hydroxyurea patients was 60%, and its was 52% for the corresponding placebo patients (P = .49). However, the estimated 5-year progression free survival rate for the correctly treated patients (continuous therapy) was 91% for the hydroxyurea group and 60% for the placebo group (P less than .06).     

放射治疗83例宫颈癌预后的相关因素

目的 :探讨放射治疗宫颈癌预后的相关因素 ,着重从肿瘤大小、疗程、局部控制情况等方面分析其与生存率的关系。方法 :83例Ⅰ、Ⅱ、Ⅲ期的宫颈癌于 1993年 4月～ 2 0 0 1年 4月在本科行首次放射治疗 ,全部病例均用60 Co远距离治疗机行盆腔外照射加192 Ir高剂量率后装治疗机行腔内照射。外照射 :中平面剂量DT 2 5～ 2 6Gy/13次后中间挡铅加量至DT 4 8～ 5 0Gy。腔内治疗 :A点的剂量DT 5Gy/次 ,DT 35Gy/ 7次。生存率计算采用Kaplan Meier法 ,差异显著性采用Log rank检验。 结果 :①局部控制情况肿瘤消退的 :一年、二年、三年、五年的生存率分别为 95 87%、77 12 %、73 0 9%、73 0 9% ,肿瘤残留的 :一年、二年、三年、五年的生存率分别为 34 2 9%、0 %、0 %、0 % ,差异有显著性意义 (χ2 =111 75 36 ,P <0 0 0 0 1)。②疗程疗程 <5 6天 :一年、二年、三年、五年的生存率分别为 93 88%、82 86 %、80 19%、80 19% ;疗程≥ 5 6天 :一年、二年、三年、五年的生存率分别为 78 95 %、30 5 5 %、2 2 91%、2 2 91%。差异有显著性意义 (χ2 =2 2 4 115 ,P <0 0 0 1)③宫颈肿瘤最大直径 <4cm :一年、二年、三年、五年的生存率分别为 95 12 %、82 86 %、79 6 7%、79 6 7% ;肿瘤最大直     

Adjuvant pelvic hyperthermia in advanced cervical carcinoma. I. Feasibility,thermometry and device comparison

From 1981 to 1989, a total of 26 women with locally or regionally advanced carcinoma of the uterine cervix were treated with radiotherapy (RT) and pelvic regional hyperthermia (HT), in the Divisions of Radiation Oncology at the University of Utah Medical Center (UU) and the Kenneth Morris Jr Cancer Hospital of the University of Southern California (USC). HT was produced by the BSD-1000 HT system and the annular phased array (AA) applicator usually driven at 60–65 MHz, or the BSD-2000 HT system and the Sigma-60 (S60) applicator usually driven at 70–85 MHz. During the HT sessions acute toxicity was common, particularly because of pain within or outside the applicator, which was power-limiting in 43% of the patients overall. Pain was more easily manipulated, but more commonly power-limiting with the S60. Systemic stress was power-limiting in 22% of patients treated with the AA, but in no patients with the S60. Detailed thermal mapping and temperature analysis were performed on 26 patients. The mean overall average intratumour temperature achieved was 41 ± 1·1 °C for 30 min; 5% and 35% of the monitored intratumour loci exceeded 43°C and 42°C, respectively. Temperatures recorded in the cervical os and proximal vagina appeared lower relative to the monitored normal structures in the region. Subacute treatment related toxicities occurred in five patients and included protracted pain (three) and superficial second degree burns (one), all of which resolved with supportive non-surgical therapy.     

临床病理参数对宫颈癌预后的影响

目的 探讨临床病理参数对宫颈鳞腺癌预后的影响。 方法 回顾性分析了702例宫颈癌患者,探讨了鳞腺癌组间构成差别,分别采用单因素和COX回归模型多因素分析了各自预后影响因素。 结果 在702例宫颈癌中,鳞癌630例,占89.4％,腺癌72例,占10.6％。与鳞癌相比,腺癌趋于年轻化、小体积、淋巴结转移,腺 癌5年生存率低于鳞癌(58.3％ VS 57.3％),但无统计学意义。多因素分析显示,组织分化、FIGO分期和淋巴结转移是鳞癌独立预后评价指标,而腺癌预后独立评价指标为FIGO分期和淋巴结转移。 结论 尽管宫颈鳞腺癌临床病理参数组间构成存在差异,但两者预后评价参数基本一样,即淋巴结转移和临床分期可能是评价两者最重要的临床、病理参数。     

The Prognosis of Patients with Stage Ib-IIb Node-Positive Cervical Carcinoma after Radical Surgery

Objective To investigate the influence of positive lymph nodes on the prognosis for patients with stage Ib-IIb cervical carcinoma. Methods Sixty-six patients with stage Ib∼IIb cervical carcinoma who underwent a radical hysterectomy and pelvic lymphadenectomy were analyzed retrospectively. The potential prognostic factors were calculated by the Cox proportional hazard model. Results The 5-year survival of the patients with pelvic lymph node metastasis was 40.7%. The Cox proportional hazard model analysis showed that cellular differentiation, the number of positive nodes and adjuvant therapy were independent prognostic factors (P< 0.05). The 5-year survival of patients with 1 positive node was higher than that of those with 2 or more positive nodes (56.5% vs 36.4%,P< 0.05). The distant metastasis rate in the former group (5.9%) was lower than the latter’s (32.7%) (P=0.05). However, there was no significant difference of pelvic recurrence between the 2 groups (P> 0.05). The 5-year survival of the patients who had no adjuvant therapy (12.6%) was much lower than that (53.7%) of those with adjuvant therapy (P< 0.05). However, there no obvious differences among the effect of adjuvant radiotherapy, chemotherapy and chemoradiotherapy (P> 0.05). Conclusion The prognosis of patients with stage lb∼llb node-positive cervical carcinoma who underwent radical surgery was poor. Adjuvant therapy can increase the survival rate, decrease the pelvic recurrence and distant metastasis.     

早期鼻咽癌单纯外照射与加近距离治疗的远期结果比较

目的随机比较单纯常规外照射与外照射加近距离治疗对早期鼻咽癌原发灶的局部控制疗效和并发症。方法对126例初治的、福州分期为T1期和部分12期(口咽、颈动脉鞘、椎前软组织受侵者除外)鼻咽癌病例进行前瞻性分组。单纯常规外照射组(RT)61例，外照射加^192Ir高剂量率近距离治疗组(RB)65例。26例T1期在疗前经抽签随机接受单纯外照射66～70Gv或外照射56Gv加近距离治疗10～16Gy，1～2次(中位剂量16Gy)；100例12期先采用常规外照射至50Gy后，行CT或MRI检查，对咽旁间隙消退满意的病例入组随机接受单纯外照射(中位剂量72Gv)或外照射(中位剂量66Gy)加近距离治疗8～24Gy，1～3次(中位剂量16Gy)。近距离治疗在外照射结束后1周进行，剂量参考点距施源器中心轴的距离为7～12mm，单次近距离照射剂量为5～8Gy／周。结果外照射结束时RT组鼻咽病灶残留6例，消退55例；RB组残留13例，?肖退46例，未评价6例。RT组鼻咽部失败8例，RB组鼻咽部失败7例(包括单独颅底失败2例)。5年鼻咽(颅底)局部控制率RT组为86％，RB组为88％。5年总生存率RT组为83％，RB组为84％(P=0．84)。放射性脑病RT组为10例(1级4例，2级6例)，RB组为7例(1级4例，2级3例)。张口困难发生率RT组明显高于RB组(26％：10％，P=0．02)。结论对早期鼻咽癌行计划性外照射加腔内近距离治疗，能获得与单纯常规外照射相近的局部控制率及总生存率，并降低外照射剂量和减低张口困难的发生率。     

术前化疗对巨块型宫颈癌ⅠB-ⅡB期的疗效评价

目的:探讨巨块型宫颈癌IB-IIB期术前应用口服氟铁龙及区域性化疗的临床意义.方法:22例宫颈肿瘤大于5cm的stageIB-IIB宫颈癌患者均接受术前口服5’-DFUR 800mg/m~2/天×14天为一疗程第29天再重复.介入化疗,导管超选择至子宫动脉,注入顺铂30mg/m~2/例,表阿霉素25mg/m~ 2/例,第2周为一疗程,共2～3疗程.然后全组病人均行宫颈癌根治术.结果:经术前化疗后宫颈局部肿瘤明显缩小,PR为100%,为彻底手术奠定基础,并使原不能手术者亦成为手术可能.结论:术前化疗对巨块型宫颈癌疗效明显.     

The role of adjunctive radiotherapy for stage I endometrial carcinoma: Preoperative vs postoperative irradiation

Eighty-five patients with clinical Stage I endometrial carcinoma were reviewed: 81% of patients had either pre-operative or post-operative radiotherapy (RT). The incidence of deep myometrial invasion (outer $\text{1}\text{3}$ of thickness) of pre-op RT vs. post-op RT group was 6% and 28% respectively; the pre-op irradiation seemed to alter the depth of myometrial invasion. Eleven patients (13%) developed recurrences: 9 of these patients (82%) had recurrences in the extrapelvis. The incidence of extrapelvic recurrence of patients with Grade 3 tumors was 29% ($\text{4}\text{14}$); those with deep myometrial invasion was 33% ($\text{4}\text{12}$). The overall 5 year survival and complication rate was 89% and 4% respectively: these results were comparable between pre-op RT and post-op RT groups. However, post-op RT offers the advantage of accurate surgical-pathologic staging and optimal individualization of adjuvant therapy. In addition, those who have deep myometrial invasion and/or Grade 3 tumors may require systemic therapy in view of high incidence of distant failures.     

局部复发鼻咽癌超分割加立体定向适形放疗的临床研究

目的：初步评价超分割外照射加立体定向适形放射剂量治疗局部复发鼻咽癌的临床疗效及毒副反应。方法：对1999～2002年收治的14例复发鼻咽癌进行超分割外照射（1．3Gy／次，2次／d，总剂量42～60Gy）加立体定向适形放射推量（4Gy／次，隔日照射，共10次，总量20Gy）的临床研究。结果：总有效率（CR＋PR）85．7％（12／14），其中完全消退（CR）64．3％（9／14），部分消退（PR）21．4％，肿瘤稳定14．3％，2年总生存率57．1％（8／14），无瘤生存率42．8％（6／14），靶区肿瘤控制率为78．6％（11／14）。结论：超分割外照射加立体定向适形放射剂量治疗局部复发鼻咽癌在临床上是可行及有效的。     

局部复发鼻咽癌超分割加立体定向适形放疗的临床研究

目的:初步评价超分割外照射加立体定 向适形放射剂量治疗局部复发鼻咽癌的临床疗 效及毒副反应。方法:对1999～2002年收治的 14例复发鼻咽癌进行超分割外照射(1.3Gy/次, 2次/d,总剂量42～60Gy)加立体定向适形放射 推量(4Gy/次,隔日照射,共10次,总量20Gy) 的临床研究。结果:总有效率(CR+PR)85.7% (12/14),其中完全消退(CR)64.3%(9/14),部分 消退(PR)21.4%,肿瘤稳定14.3%,2年总生存 率57.1%(8/14),无瘤生存率42.8%(6/14),靶 区肿瘤控制率为78.6%(11/14)。结论:超分割 外照射加立体定向适形放射剂量治疗局部复发 鼻咽癌在临床上是可行及有效的。     

Ⅱb～Ⅲb期宫颈癌术前介入联合手术治疗及其临床意义

目的 探讨Ⅱb～Ⅲb期宫颈癌术前髂内动脉持续化疗栓塞联合手术治疗及其临床意义。方法 52例Ⅱb～Ⅲb期宫颈癌行髂内动脉持续化疗栓塞105次并联合手术44例、放疗8例。结果 局部病灶变化达80.8％的反应率，44例宫颈癌根治手术中残端无癌细胞，宫旁病灶为大量坏死组织，6例阳性淋巴结为坏死组织。结论 Ⅱb～Ⅲb期宫颈癌术前介入联合手术治疗是有效的方法。能提高手术的切除率，改善预后，成为治疗该病的一种新手段，具有重要的临床意义。     

Split-course radiation therapy of carcinoma of the base of the tongue: Results of a prospective national collaborative clinical trial conducted by the radiation therapy oncology group

One hundred forty-one patients with carcinoma of the base of tongue were randomized to receive either continuous course radiotherapy (6600 rad in $\text{30}\text{33}$ fractions over 7–8 weeks) or split course therapy (3000 rad in 10 fractions over 2 weeks, a three-week rest, 3000 rad in 10 fractions over 2 weeks). Both treatment groups tolerated the treatment well, but the continuous course group required more treatment modifications. The results of therapy, as judged by control of primary tumor, control of metastatic lymph nodes, time to failure and overall survival were comparable in the two treatment groups.