Combined radiotherapy and chemotherapy for advanced carcinoma of the cervix

Until recently the use of cytotoxic drugs in the treatment of squamous carcinoma of the cervix has been limited to patients with local recurrence after primary therapy or with distant metastases. The effectiveness of some cytotoxic drugs, especially cisplatin, in producing tumour regression in this group of patients with a poor prognosis, has encouraged the use of chemotherapy at an earlier stage of the disease process. Since 1979 patients with FIGO IIb squamous carcinoma of the cervix extending more than half-way to the pelvic side-wall and Stages III and IV disease have been treated with a combination of cisplatin or methotrexate and radiotherapy. The complete remission rate of Stage III tumours was 89% with a local recurrence rate of only 8%. In patients with advanced Stage IIb disease only 44% achieved complete remission and three patients with Stage IV disease failed to respond. The projected 5-year survival rate is 66% for patients with Stage III disease and 49% for all patients. The results of this combined treatment are presented and discussed and the suggestion made that chemotherapy combined with radiotherapy can be safely used to advantage in patients at high risk of local relapse.     

综合治疗儿童髓母细胞瘤33例临床分析

目的回顾性分析髓母细胞瘤的临床特点,探讨合理治疗方案,分析预后影响因素。方法 2004年8月-2007年12月共收治髓母细胞瘤术后患儿33例。术后3周内开始放疗,先予以全脑全脊髓28~36Gy,再予瘤床处三维适形局部补量至总量50~54Gy,常规分割剂量1.8~2.0Gy/次;为减轻晚反应,部分患儿采用超分割照射技术(1.0Gy/次、2次/d);所有患者在6~8周内完成放疗。全脑全脊髓放疗完成后行1个周期同步化疗,全部放疗结束后再进行序贯化疗3~5个周期;化疗方案为洛莫司汀+长春新碱+顺铂或异环磷酰胺+卡铂+依托泊苷。根据肿瘤是否转移、残存及残存肿瘤大小将患儿分为两组:低风险组(n=24):无转移、肿瘤全切或近全切(残留肿瘤体积≤1.5cm3);高风险组(n=9):已有转移或残留肿瘤体积>1.5cm3。比较两组患者的3年生存率。结果术后残留病灶患儿的放化疗有效率为90.9%(10/11),全组完全缓解(CR)93.9%(31/33),部分缓解(PR)3.0%(1/33),稳定(SD)3.0%(1/33)。所有患者中位生存时间51个月,3年总生存率和无病生存率分别为78.8%、75.8%。高风险和低风险患儿的3年生存率分别为33.3%和95.8%(P<0.01)。不良反应主要为血液系统和消化系统的毒性反应:Ⅲ-Ⅳ度骨髓抑制发生率为21.2%(7/33),恶心发生率87.9%(29/33),伴呕吐者66.7%(22/33)。结论儿童髓母细胞瘤的诊断不难,首选手术治疗,术后联合放化疗的总体疗效好,严重不良反应的发生率较低。肿瘤清除程度是影响预后的因素之一。     

Combined intra-arterial chemotherapy and radiotherapy in inoperable non-small cell bronchial carcinoma]

The five years survival rates of patients with non-operable non-small cell lung carcinoma are between 6% and 9%. Multiple attempts have been made to improve the response rate and the survival of these patients with different chemo- and radiotherapy schemes. The systemic chemotherapy with cisplatin-vindesine is until now one of the most active treatments with a response rate of 40%, but it is limited because of its side effects and toxicity. Eleven patients are treated one to four times with an intraarterial infusion of 3 mg/m2 vindesine and 20 mg/m2 cisplatin into the tumor-feeding bronchial artery combined with a simultaneous radiotherapy (60 Gy). Until now no major side effects occurred and the systemic toxicity was insignificant. An objective tumor response was encountered in 7/11 patients. The intraarterial chemotherapy combined with radiotherapy is strictly local and therefore effective especially in patients with limited or locally advanced disease.     

Combined chemotherapy-radiotherapy study of small cell bronchial carcinoma: chemo-/radiotherapy vs radio-/chemotherapy

The authors studied the effect of a chemo-/radiotherapy or radio-/chemotherapy on 52 cases of microcellular bronchial carcinoma, classification "limited disease". The survival curves were slightly better for the patients submitted to primary chemotherapy, but the difference was not statistically significant, and the curves coincided again after 18 months. 60 to 80% of the patients had no complaints or only unimportant complaints during more than half of their survival time. In 23 patients with "extensive disease" who received only a symptomatic therapy or a combined palliative chemotherapy, chemotherapy had a slightly better effect, but this was not statistically significant.     

The combination of radiotherapy and chemotherapy: a review

The association of radiotherapy (RT) and chemotherapy (CT) is clearly beneficial in tumours which are both chemosensitive and radiosensitive (Tubiana et al. 1987). However, contrary to the expectations, in most solid tumours this association did not lead to significant progress in long-term survival. In head and neck cancers, for example, despite a large number of controlled clinical trials, there is not yet a clear-cut demonstration of any increase in survival (DeVita et al. 1986, Tannock and Browman 1986, Taylor 1987, Tubiana et al. 1985). These disappointing results are probably due to two factors: (1) the insufficient effectiveness of the available drugs on most solid tumours; (2) the cumulative toxic effects of radiation and drugs on the normal tissues, which limits the dose of both modalities in combined treatments.     

Monitoring chemotherapy and radiotherapy of solid tumors

PET imaging with the glucose analog fluorodeoxyglucose (FDG-PET) has been evaluated in numerous studies to monitor tumor response in patients undergoing chemo- and radiotherapy. The clinical value of FDG-PET for differentiation of residual or recurrent viable tumor and therapy-induced fibrosis or scar tissue has been documented for various solid tumors. Furthermore, there are now several reports suggesting that quantitative assessment of therapy-induced changes in tumor FDG uptake may allow prediction of tumor response and patient outcome very early in the course of therapy. In nonresponding patients, treatment may be adjusted according to the individual chemo- and radiosensitivity of the tumor tissue. Since the number of alternative treatments for solid tumors (e.g., second-line chemotherapy agents, protein kinase, or angiogenesis inhibitors) is continuously increasing, early prediction of tumor response to chemotherapy and radiotherapy by FDG-PET has enormous potential to "personalize" treatment and to reduce the side-effects and costs of ineffective therapy.     

Combined bleomycin and radiotherapy in oral cancer

A clinical trial comparing Bleomycin (BLM) plus radiation against radiation alone is reported. One hundred and fifty-seven previously untreated T3 and T4 and N0, N1 or N2 buccal squamous cell carcinomas were entered. Eighty-four of these received the combined therapy and 73 were controls. Cobalt-60 teletherapy using two opposing fields was employed. BLM was administered intra-arterially in 42 patients, intravenously in 22 patients and intramuscularly in 20 patients. The 73 controls received physiological saline as a placebo. Total clinical healing of the lesion within the volume of irradiation eight weeks after the end of radiotherapy was termed a favourable response. Anything else was a failure. Five-year recurrence-free rates and disease-free survival were also evaluated. The favourable response rate in the study group was 78.6% and in the control 19.1%. The corresponding recurrence-free rates and five-year survival rates were 71.8% and 17%, and 65.5 and 23.5% respectively. The main toxic features were acute mucositis, pneumonitis and dermatitis.     

Nasopharyngeal carcinoma: a review of cases treated by radiotherapy and chemotherapy

Between 1965 and 1983, 52 cases of carcinoma of the nasopharynx were treated with radiotherapy alone and 14 treated with combination chemotherapy containing cisplatin followed by a radical course of radiation. Before 1981 all cases were treated by radiotherapy alone with a variety of dose and fractionation regimes. The actuarial overall 3 year survival for these cases was 35%. Twelve of the 14 (86%) who received chemotherapy responded, and in two there was complete disappearance of disease before the radiotherapy. The 3 year survival for those receiving chemotherapy and radiotherapy was 86%. The possible reasons for this apparent improvement are discussed.     

Adjuvant therapy in breast cancer (high risk). Randomized study: radiotherapy versus combination radiotherapy and chemotherapy

108 patients with high risk stage of a mammary carcinoma (four or more positive axillary lymph nodes) were submitted after surgery to a prospectively randomized study: a postirradiation in three series with additional administration of tamoxifen was opposed to a reduced-dose irradiation and subsequent simultaneous combination of polychemotherapy and irradiation. In patients with an age of less than 50 years, the combination of chemotherapy and radiotherapy caused a significant prolongation of the recurrence-free interval (greater than 57 months versus 12,75 months). The comparison with literature shows that an average interval of 39.1 months without recurrences for the total group of patients treated with combination therapy corresponds to the result of a high-dose adjuvant CMF therapy. With respect to mean life expectancy, there was no significant difference between both groups of randomization.     

Intraoperative radiotherapy and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy

Purpose

Treatment of rectal cancer has markedly improved since the introduction of neoadjuvant strategies and better surgical techniques. However, treatment remains troublesome for patients with locally advanced rectal cancer (LARC) or with peritoneal carcinomatosis (PC). Patients presenting with LARC may now benefit from the integration of intra-operative radiotherapy (IORT) into multimodality treatment. Selected patients with PC now undergo cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) resulting in improved survival. Some patients present with locally advanced disease and synchronous peritoneal carcinomatosis and fulfill the eligibility criteria for both HIPEC and IORT, raising the question whether the combined application of both modalities within one operative procedure is feasible.

Case series

This report includes five consecutive cases of rectal cancer patients presenting with LARC and synchronous PC who were treated with a multimodality treatment including IORT and HIPEC after cytoreductive surgery. Postoperative complications and survival are described.

Results

The combination of cytoreductive surgery with HIPEC and IORT appeared to be feasible and well tolerated. The observed complications did not differ from the morbidity associated with extensive pelvic surgery without HIPEC or IORT. No inhospital mortality occurred. One patient died after 11 months of recurrent disease. All other patients are currently alive with one patient already surviving 38 months.

Conclusion

The current case series shows that a multimodality treatment containing IORT and HIPEC is feasible and safe with promising survival rates. This strategy may, therefore, be considered in selected rectal cancer patients presenting with both LARC and synchronous PC.     

Results of radiotherapy and chemotherapy in small-cell bronchial carcinoma

At the Radiotherapeutic Department of the Faculty of Medicine in Istanbul, 35 masculine patients with microcellular bronchial carcinoma, limited disease, were treated for two years, i.e. between 1980 and 1981, with a combination of radiotherapy and chemotherapy. Nine out of these patients are tumor-free after at least 46 months, i.e. about four years. This corresponds to a tumor-free survival rate of 25.7%.