康赛迪胶囊对食管癌放疗患者细胞免疫功能的影响

目的　观察中药复方制剂康赛迪胶囊对食管癌患者放疗前后细胞免疫功能的影响。方法　采用FACSCalibur流式细胞仪 ,SimulSETv3 1分析软件 ,分别检测 2 0例食管癌患者在放疗 6 0Gy前后 (对照组 )和口服康赛迪同时放疗 6 0Gy前后 (实验组 )患者外周血NK细胞活性、T淋巴细胞亚群 (CD3+、CD4 +、CD8+)、CD4 +/CD8+、B淋巴细胞 (CD19+)、NK淋巴细胞 (CD16 +,CD5 6 +)水平。结果　二组患者放疗前外周血NK细胞活性、CD3+、CD4 +、B淋巴细胞百分数、CD4 +/CD8+的平均值均低于健康人参考值 ,其中CD4 +细胞和B淋巴细胞明显下降 ,CD8+细胞明显升高。对照组患者放疗 6 0Gy后 ,除CD8+细胞和NK淋巴细胞百分数稍有升高外 ,其他细胞均略有下降 (P >0 0 5 )。实验组患者在治疗后CD3+、CD4 +、NK淋巴细胞百分数、CD4 +/CD8+明显升高 ,并明显高于对照组 (P <0 0 5或P <0 0 1)。结论　食管癌患者在放疗前后细胞免疫功能持续低下。放疗 6 0Gy后患者细胞免疫功能受到轻度抑制 ,康赛迪可以明显改善食管癌患者放疗后的细胞免疫功能状态。提示食管癌患者在放疗的同时应加强免疫治疗 ,以改善患者的免疫抑制状态。     

Effect of blood transfusion during radiotherapy on the immune function of patients with cancer of the uterine cervix: role of interleukin-10

: To analyze prospectively the effects of blood transfusion administered during radiotherapy (RT) on the immune function of patients with locally advanced cervical cancer.

: In a total of 15 patients, 7 transfused and 8 untransfused, lymphocyte populations, including CD3+, CD4+, and CD8+ T-cell subsets, B cells (CD19+), and natural killer (NK) cells (CD56+, CD16+, CD3−) were studied before (i.e., time 0), during (i.e., times 1 and 2), and after (i.e., time 3) therapy. Expression of the early (CD25) and late (HLA-DR) activation markers on CD3+ T cells, the intracellular levels of perforin in CD8+ and CD56+ cells, and interferon (IFN)-γ, interleukin (IL)-2, and IL-4 in CD4+ and CD8+ T cells were also measured. NK cell cytotoxicity against the NK-sensitive target K-562 cells and CD8+ T-cell-directed cytotoxicity against OKT3 hybridoma cells were also assessed. Finally, the plasma levels of the immunoregulatory cytokine IL-10 were analyzed by enzyme-linked immunosorbent assay.

: The mean absolute number of all lymphocyte subsets compared with pretreatment levels decreased significantly during RT of both transfused and untransfused patients (p >0.001), with no detectable differences between the two groups in terms of total lymphocytes or relative numbers of CD3+ and CD4+ T cells, CD56+ NK cells, or CD19+ B cells. In contrast, concomitant with an inversion of the CD4/CD8 ratio, a significant increase in the number of CD8+ T cells at time 2 and CD3+ T cells, CD8+ T cells, and NK cells at time 3 was found in the transfused patients compared with the untransfused group. The percentages of CD25+/CD3+ T cells and HLA-DR+/CD3+ T cells increased during RT of the untransfused patients, but CD3+ T cells showed decreased CD25 expression and increased HLA-DR expression in the transfused group. An increase of CD8+ IFN-γ+ T cells with a concomitant decrease in CD8+ IL-2+ T cells was found in the transfused vs. untransfused group, and no differences were noted in the percentage of CD4+ IFN-γ+ T cells and CD4+ IL-2+ T cells. The proportion of perforin-positive CD8+ and CD56+ cells was higher in the transfused group than in the untransfused group. However, CD56+ cells and CD8+ T cells from the transfused patients showed markedly diminished cytotoxic function. Finally, IL-10 was detected only in the plasma of the transfused patients.

: Blood transfusion during primary RT for cervical cancer profoundly alters the magnitude and characteristics of radiation-induced immunosuppression. Elevated serum IL-10 in transfused patients may play a role in the disregulation of lymphocyte function, in particular, the depression of NK- and T-cell cytotoxicity. Investigation of alternatives to blood transfusion during RT that do not diminish host immunity is warranted.     

Results of radiotherapy alone in 581 patients with Stage II carcinoma of the uterine cervix

From January 1976 to December 1978, 581 previously untreated patients with Stage II carcinoma of the uterine cervix were treated by radiotherapy alone in nine departments of radiotherapy in France. This retrospective analysis was undertaken in an attempt to evaluate the therapeutic results and prognostically significant factors. The initial clinical staging and the therapeutic guidelines were as outlined at the U.T. M. D. Anderson Hospital in Houston; all our patients were treated by standardized protocols combining external beam irradiation and intracavitary irradiation with cesium sources. The overall locoregional control rate was 83.2%, with total disease control of 74.5%. Uncorrected actuarial survival rates are 76% at 3 years and 68% at 5 years. The incidence of severe posttherapeutic complications is 7.2%. Clinical substaging, patient's age at the time of the diagnosis, lymphangiogram findings, and tolerance to external irradiation were all found to have prognostic significance. According to those findings, the possibilities of improving the results are discussed.     

Prognostic significance of pretherapeutic and therapeutic factors in patients with advanced cancer of the uterine cervix treated with radical radiotherapy alone.

The prognostic importance of various pretherapeutic and therapeutic factors was analysed in a group of 413 cervical cancer patients with stage IIB (183 pts) and IIIB (230 pts) treated with radical radiotherapy, which consisted of external irradiation and intracavitary brachytherapy. Univariate analysis of pretherapeutic factors revealed the prognostic significance of patient age, history of abortion, stage, haemoglobin and hematocrit levels. Five-year overall survival rate in stage IIB patients was 51%, in stage IIIB 40% and the respective rates for local control at each stage were 61%, and 46%. Univariate analysis of therapeutic factors showed that survival and local control rates increased with the dose, but a significant difference was found only in the case of a paracentral (point A) dose. In a multivariate analysis only patient age, abortions, and clinical stage appeared to have a significant and independent impact on survival. Linear regression analysis results indicated that prolongation of treatment time between 33 and 108 days caused a loss of local control of 0.36% per day.     

Patterns of failure in carcinoma of the uterine cervix treated with definitive radiotherapy alone.

The purpose of this retrospective study was to evaluate the patterns of failure for the patients treated with definitive radiotherapy, and to discuss future treatment strategies for the uterine cervical cancer. From 1986 to 1995, 177 patients with stages I-III cervical cancer treated with a combination of two-axial conformal radiotherapy and radium brachytherapy were analyzed. The first treatment failures were pelvic failure in 11%, and distant metastases (DM) in 16% of the 177 patients. Paraaortic lymph nodes (PAN) were the most frequently metastatic regions (71%). In the pelvic control group, DM were in 6% of patients for stages I-II, and in 32% of patients for stage III. In the pelvic failure group, DM were in 75% of patients for stages I-II, and in 19% of patients for stage III. In stages I-II, the DM rate was significantly correlated with pelvic tumor control. However, there was no correlation in stage III. To improve survival, it is important to increase the pelvic tumor control rate for patients with stage I-II, and to increase the pelvic tumor and metastatic control rate in stage III. Additional treatments such as chemotherapy and/or PAN irradiation using conformal radiotherapy are required in stages I-II with locally bulky tumor and in stage III.     

Results of external-beam radiotherapy alone in invasive cancer of the uterine cervix: a retrospective analysis

AimsIn this retrospective audit, we describe the results of external-beam radiotherapy (EBRT) alone in patients with invasive cancer of the cervix treated at our centre.Material and MethodsWe included 146 patients with invasive cancer of the cervix who were treated with EBRT to a total dose of 60–66 Gy between January 1996 and December 2001. None of these patients were suitable for intracavitary radiotherapy (ICRT) after a median dose of 46 Gy. A boost dose of 14–20 Gy was given after a gap of 2–4 weeks. Most patients belonged to stage IIIB (n = 124).ResultsFollow-up of patients at risk ranged from 19 to 89 months (median 48 months). One hundred and thirty-six patients (93.2%) received EBRT to a dose of 66 Gy, and 10 patients (6.8%) received 60 Gy. Overall treatment time (OTT) ranged from 56 to 160 days (median 78 days). At completion of 46 Gy of EBRT, 63 patients achieved partial response and 83 patients had stable disease. Five-year overall survival, disease-free survival (DFS) and pelvic control were 15.1% (median 9 months), 11.6% (median 5 months) and 21.9% (median 6 months), respectively. Factors found to affect 5-year pelvic control in univariate analysis by Kaplan–Meier method were response to EBRT at 46 Gy (partial response 36.5% and stable disease 10.8%), age (≥50 years 28.8% and <50 years 13.6%) and OTT (<90 days 26.5% and ≥90 days 12.5%). For DFS and overall survival, response to EBRT was the only factor that was significant in univariate analysis. In multivariate analysis by Cox's proportional hazard model, response to EBRT was the only factor to influence pelvic control (P = 0.007), DFS (P = 0.01) and overall survival (P < 0.001).ConclusionsOverall outcome of patients in whom ICRT was not given remains less than satisfactory. Response to EBRT emerged as the most important factor to predict all clinical outcomes. To improve upon the dismal results of EBRT alone, we will have to decrease the OTT and consider concurrent chemo-radiation with cisplatin.     

Concomitant radiochemotherapy vs radiotherapy alone in patients with head and neck cancer

The primary objective of the present randomized phase III trial was to compare the 3-yr survival rate of patients treated with standard fractionated radiotherapy (RT) alone or with the same RT concomitantly with cisplatin (DDP) or carboplatin (Cb). From January 1995 until July 1999, 124 patients with histologically proven locally advanced non-nasopharyngeal head and neck cancer (HNC) were randomized to receive either RT monotherapy (70Gy, Group A) or the same RT concomitantly with DDP (100 mg/m² on d 2, 22, 42, Group B) or Cb (7 AUC on d 2, 22, 42, Group C). There were no significant differences in complete response rates between patients treated with RT alone or combined chemoradiotherapy. However, median time to progression (TTP) and overall survival (OS) were significantly longer in patients treated with concomitant chemoradiotherapy. Thus, median TTP was 6.3, 45.2, and 17.7 mo in groups A, B, and C respectively (p=0.0002). Similarly, median OS was 12.2, 48.6, and 24.5 mo, respectively (p=0.0003). At 3 yr follow-up, 17.5% of patients in group A were alive compared to 52% in group B and 42% in group C (p<0.001). Patients treated with concomitant chemoradiotherapy experienced more frequently severe hematological toxicity. Also, severe nausea/vomiting was more pronounced in group B, as expected. The present study clearly demonstrated that concomitant chemoradiotherapy with platinum analogs significantly prolongs 3-yr survival and median OS in patients with locally advanced HNC compared to conventional RT alone. This work was accepted for oral presentation at the 2003 Annual Meeting of the American Society of Clinical Oncology. May 31–June 3, Chicago, IL, USA.     

Interstitial radiotherapy for recurrent cancer of the uterine cervix

Thirty-seven patients with recurrent cancer of the uterine cervix were treated with interstitial radiotherapy between 1966 and 1983 at NIRS. The 1-, 3- and 5-year survival rates after the salvage treatment were 57%, 30% and 24%, respectively. A local control rate of more than 80% was achieved in smaller-than-thumb-sized lesions. However, the rates decreased to 27% in larger tumors. The local control rate of all patients was 58%. A dosage of 60-70 Gy was required to control the smaller lesions, while the larger ones were difficult to control irrespective of the dosage. Therefore, early detection of recurrent cancer is most important for this treatment.     

Abdominal radiotherapy for cancer of the uterine cervix and endometrium

From 1973 through 1985, 49 women received postoperative open-field whole abdominal radiotherapy as primary management for peritoneal metastases from uterine cancer. The 5-year relapse-free rate was 63% in women with endometrial carcinoma, and two prognostic subsets were identified. Five-year relapse-free rates fell from 77% in women with spread to the adnexa or peritoneal fluid to 36% in women with macroscopic spread of cancer beyond the adnexa. Any peritoneal spread of cervical carcinoma yielded a 3-year relapse-free rate of 31%. Although abdominal spread of cervical cancer was associated with other poor prognostic factors, peritoneal metastases frequently occurred in otherwise early endometrial cancer. Four percent of patients developed small bowel obstruction requiring surgical intervention. The utility and limitations of whole abdominal radiation are discussed.     

Results of treatment of uterine cervix cancer by radiotherapy

The results of treatment of uterine cervix cancer by radiotherapy alone in 259 patients in the period January 1973 to December 1984 are reported. They are analyzed according to patients age, stage, tumor volume, extent of parametrial infiltration, hydronephrosis and nodal status. It is shown that age, tumor volume, extent of parametrial invasion and nodal metastases are the main prognostic factors. Analysis of pelvic failures shows that external radiotherapy followed by curietherapy seems to be the best method for patients with T2b and T3b tumors of small volume (less than 60 mm in diameter), particularly when parametrial infiltration is limited. Patients with T2b tumors of large volume (barrel shaped) seem to need a more aggressive approach, and a higher number of complications are therefore expected. Patients with T3b and massive parametrial infiltration, with T4 and nodal metastases need new and different approaches, possibly including adjuvant chemotherapy.     

放疗对食管癌患者免疫功能及预后的影响

目的：观察食管癌患者放疗前后免疫功能的动态变化,探讨与其相关的临床预后因素。方法选取2010年1月至2013年12月在南通大学第二附属医院放疗科就诊的食管癌放疗患者90例,分别于放疗前、放疗结束及放疗后3个月使用流式细胞仪检测患者外周血 T 淋巴细胞亚群及 NK 细胞比例,以30例本院健康体检者外周血人群为对照观察其变化。分析患者放疗前后免疫功能变化与临床特征及预后的关系。结果食管癌患者放疗前外周血 CD4＋、CD8＋、CD4＋／CD8＋比值、NK 细胞百分比分别为28．23％±8．22％、31．79％±7．61％、0．93±0．34、11．37％±4．57％,与对照组（36．03％±9．71％、27．26％±7．70％、1．34±0．27、15．31％±5．13％）相比,差异均有统计学意义（t ＝4．292,P ＝0．000;t ＝2．811,P ＝0．006;t ＝5．894,P ＝0．000;t ＝3．965,P ＝0．000）;放疗前外周血 CD3＋细胞百分比为58．13％±9．46％,与对照组（60．06％±8．67％）相比,差异无统计学意义（t ＝0．998,P ＝0．325）。放疗后3个月免疫指标 CD3＋（59．27％±9．92％）、CD4＋（30．51％±9．04％）、CD8＋（29．79％±6．98％）、NK 细胞（10．62％±4．43％）逐渐恢复到放疗前水平（t ＝0．789,P ＝0．431;t ＝1．769,P ＝0．079;t ＝1．837,P ＝0．068;t ＝1．113,P ＝0．267）。放疗后免疫功能改变（CD4＋、CD8＋、CD4＋／CD8＋、NK 细胞）与是否存在骨髓抑制（t ＝4．050,P ＝0．001;t ＝2．180,P ＝0．015;t ＝2．130,P ＝0．020;t ＝3．520,P ＝0．003）及照射体积大小（t ＝5．170,P ＝0．000;t ＝3．350,P ＝0．026;t ＝8．750,P ＝0．000;t ＝2．490,P ＝0．043）有关。生存分析显示：放疗后3个月免疫功能恢复良好的患者其中位生存时间优于恢复不良者（23个月∶17个月,χ2＝6．820,P ＝0．009）。结论食管癌患者放疗前处于免疫功能抑制状态,放疗实施会进一步加重免疫抑制,其加重程度与骨髓抑制及照射体积相关;放疗后3个月患者免疫功能有所恢复,恢复良好者预后较好。     

局部进展期直肠癌术前新辅助治疗疗效分析

目的 观察术前同期放化疗或术前单纯放疗在T3、T4期或影像学淋巴结阳性直肠癌患者治疗中的疗效和安全性.方法 回顾分析2000 -2009年收治的141例局部进展期或影像学淋巴结阳性的直肠癌患者资料,其中术前同期放化疗97例,术前单纯放疗44例.放疗采用二维或三维技术,化疗采用4种方案.结果 随访率为91.5％,随访满3、5年者分别为106、68例.降期率达59.0％ (82/139),保肛手术率达65.5％ (91/139).3、5年总生存率分别为85.8％、65.7％,局部复发率分别为9.2％、14.1％,转移率分别为33.8％、45.8％.术前同期放化疗患者中位无瘤生存期优于术前单纯放疗(51:31个月,x2=12.88,P=0.000).肿瘤降期患者在远处转移时间上迟于未降期患者(60:29个月,x2=14.65,P=0.000).急性不良反应多为1、2级,伤口愈合延迟及吻合口瘘发生率低.结论 术前同期放化疗或术前单纯放疗能明显降低肿瘤分期、提高手术保肛率,不良反应小且绝大多数患者可耐受.     

Carcinoma of the uterine cervix treated with external irradiation alone

One hundred and four out of 2701 patients with carcinoma of the uterine cervix were treated with a curative intent by external irradiation alone at the National Cancer Center Hospital from 1962 to 1979. All patients were judged inappropriate for the combined treatment of intracavitary and external irradiation, which was the treatment of choice for patients with advanced carcinoma of the uterine cervix in the hospital. The 5-year survival rate was 17% overall and 36, 17, and 5% for patients with Stage II, III, and IV disease, respectively. The local control rate was 20%, at 2 years, for all patients. Major complications were observed in five patients. There were no major complications in patients given a total dose of less than 115 in the Time Dose Fractionation factor (TDF). External irradiation combined with interstitial irradiation and/or hyperthermia is being considered to improve the results.     

Phase I study with weekly cisplatin-paclitaxel and concurrent radiotherapy in patients with carcinoma of the cervix uteri.

Background.Cisplatin and paclitaxel are active in cervical cancerand both are able to potentiate the effects of radiotherapy. In this study weevaluated the maximum-tolerated dose (MTD) of paclitaxel in combination witha fixed dose of cisplatin when given weekly concurrently with pelvicradiotherapy to patients with carcinoma of the cervix uteri. Patients and methods:Eighteen patients with cervical cancer wereenrolled in this study. Cisplatin (30 mg/m²) and paclitaxel(starting dose 40 mg/m²; 5 mg/m² escalation per level)were given on day 1 of radiotherapy and then weekly for six times.Radiotherapy was given to the pelvis with a four-field box technique for fivedays each week. Patients received 65 Gy in 1.8 Gy fractions. Cohorts of threepatients were enrolled at each level and three further patients were includedif one or two dose-limiting severe adverse events (SAE) were recorded. SAE wasdefined as grade 3 or 4 nonhematologic toxicity, excluding nausea or vomitingand alopecia, grade 4 neutropenia or thrombocytopenia, and prolonged (>1week) neutropenia or thrombocytopenia. Results:Four levels were studied (paclitaxel 40, 45, 50, 55mg/m²) with three, five, four and six patients enrolled,respectively. The MTD of paclitaxel was found at 50 mg/m²/wk andcisplatin 30 mg/m²/wk. Diarrhea was the dose-limiting toxicity.Thirteen patients were evaluable for response: seven complete and five partialresponses were obtained with an overall response rate of 92.3%. Conclusions:The MTD of paclitaxel is 50 mg/m²/wk whenassociated to cisplatin 30 mg/m²/wk and concurrent pelvicradiotherapy. Diarrhea is the dose limiting side effect. Preliminary datasuggest that concurrent chemoradiotherapy with paclitaxel and cisplatin couldbe a very active treatment for patients with locally advanced carcinoma of thecervix.