Is Prophylactic Para-Aortic Irradiation Worthwhile in the Treatment of Advanced Cervical Carcinoma? Results of a Controlled Clinical Trial of the EORTC Radiotherapy Group

Haie, C.; Pejovic, M.H.; Gerbaulet, A.; Horiot, J.C.; Pourquier, H; Delouche, James C.; Heintz, J.; Drune, D.; Fenton, J.; Pizzi, Giuseppe; Bey, P.; Brossel, R.; Pillement, P.; Volterrani, F; Chassagne, D.

doi:10.1016/0958-3947(88)90071-4

Cited by 13 publications

(19 citation statements)

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“…As expected, two DNA bands of 6.2 and 5.0 kb were observCervical cancers are treated by surgery, radiation and cytotoxic drugs (Friedlander et al, 1983;Haie et al, 1988;McGuire et al, 1989). Treatment depends on prognosis which is determined by clinicopathological parameters of which the most important are clinical stage at diagnosis and nodal status (Pejovic et al, 1981).…”

Section: Resultssupporting

confidence: 57%

Expression of anionic glutathione S transferase (GSTπ) gene in carcinomas of the uterine cervix and in normal cervices

Riou

Barrois²,

Zhou³

1991

Br J Cancer

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SummaryThe aim of the present study was to analyse in invasive carcinomas of the uterine cervix, the anionic glutathione S transferase (GSTi) gene, possibly implicated in the drug resistance of human cancers. Total RNA preparations obtained from invasive cervical cancers (106 specimens), carcinomas in situ (CIS) (three specimens) and normal cervical epitheliums (24 specimens) were analysed by Northern (Pastan & Gottesman, 1987;Moscow & Cowan, 1988;Endicott & Ling, 1989;D'Arpa & Liu, 1989;Beck, 1989;Giovanella et al., 1989;Tew, 1989 (Beck, 1989;Giovanella et al., 1989). Another mechanism of action involving glutathione S transferase was described in cancer cells resistant to drugs as different as cis-platinum, alkylating agents and anthracyclines (Tew, 1989). The anionic isoenzyme glutathione S transferase (GSTx) which belongs to a complex group of drug-detoxifying enzymes, was present at high levels in the MCF7 breast cancer cell line resistant to Doxorubicine (DXR) together with high levels of MDRI transcripts (Batist et al., 1986;. Although the precise role of GST7 in the development of resistance is not known, its expression may be one among the numerous phenotypic and biochemical changes which accompany drug resistance in some cancers.Patients with invasive carcinoma of the uterine cervix are treated by surgery, radiation and/or chemotherapy (Friedlander et al., 1983;McGuire et al., 1989 Materials and methodsCervical cancers and normal cervical epitheliums One hundred and six specimens of invasive cervical cancer were obtained by biopsy or rarely by surgical excision from untreated patients (93 primary tumours and 5 node metastases) and from treated patients (six recurrent tumours and two liver metastases). These treated patients have received external beam radiotherapy (RX) and/or drug regimen (DR) composed of cis-platinum, Methotrexate, Chlorambucil and Vincristine (Table I). Three specimens of carcinoma in situ (CIS) were also obtained at surgery. Specimens of normal cervical epithelium were obtained from 18 patients treated by surgery for fibroma of the uterine corpus and from six patients with adjacent primary cervical cancers. Tumour and cell samples were immediately stored in liquid nitrogen.DNA and RNA preparations DNAs and total RNAs were prepared from the same tissue samples (about 100 mg) by the guanidinium isothiocyanateCsCl gradient method (Maniatis et al., 1982;Sheng et al., 1990

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Section: Resultssupporting

confidence: 57%

Expression of anionic glutathione S transferase (GSTπ) gene in carcinomas of the uterine cervix and in normal cervices

Riou

Barrois²,

Zhou³

1991

Br J Cancer

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“…7 Extended-field radiation itself incurs a high rate of intestinal morbidity 8,9 and prophylactic treatment of the para-aortic region has not been conclusively shown to provide any survival benefit. 10,11 Unfortunately, in patients with unresectable disease, cervical biopsy material alone does not provide reliable histopathologic features to predict the presence of lymphatic invasion, nodal metastasis, or patient outcome to guide in therapy.…”

mentioning

confidence: 99%

Low podoplanin expression in pretreatment biopsy material predicts poor prognosis in advanced-stage squamous cell carcinoma of the uterine cervix treated by primary radiation

et al. 2006

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Lymphatic invasion and nodal metastasis are predictors of poor outcome in cervix carcinoma. We have recently found that low podoplanin immunoreactivity in cervix carcinoma correlated with the presence of lymphatic invasion and nodal metastasis. In the current study, we examined whether podoplanin expression in pretreatment cervical biopsies can predict the presence lymphatic invasion, nodal metastasis, and outcome in advanced-stage tumors treated by nonsurgical means. Podoplanin expression was analyzed by immunohistochemistry in 48 cervical biopsies and corresponding hysterectomy specimens of early-stage invasive squamous cell carcinoma and in 74 pretreatment biopsies from advanced-stage tumors treated with primary radiation. We found a highly significant correlation between podoplanin expression obtained in biopsy and corresponding hysterectomy materials (r ¼ 0.8962, Po0.0001). Low podoplanin expression showed a significant correlation with lymphatic invasion (Po0.0001) and nodal metastasis (P ¼ 0.0058). Low podoplanin expression in pretreatment biopsy material showed a significant correlation with poor disease-free (P ¼ 0.0009) and overall (P ¼ 0.0002) survival in advanced-stage tumors. Our results suggest that in advanced-stage cervix carcinomas treated by radiation, when traditional prognostic indicators are not available and treatment decisions are based on biopsy material and clinical staging parameters, examination of podoplanin expression in pretreatment biopsy material may be a useful marker to predict lymphatic metastasis and patient outcome. Prospective studies involving larger numbers of patients are needed to further evaluate the clinical utility of examination of podoplanin expression in patients with cervix carcinoma.

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“…IIb and III), does not show any bene®t in survival, local control or overall distant metastases [14]. There was a clear increase in the incidence of severe digestive complications in patients receiving para-aortic irradiation (9 vs. 4.8%) [14,41]. However, considering the reduced incidence of para-aortic and distant metastases in patients without recurring tumor at pelvic sites, if treated with extended ®elds, the authors proposed to treat para-aortic nodes where there is a high probability of local control [14].…”

Section: Radiotherapymentioning

confidence: 87%

“…There was a clear increase in the incidence of severe digestive complications in patients receiving para-aortic irradiation (9 vs. 4.8%) [14,41]. However, considering the reduced incidence of para-aortic and distant metastases in patients without recurring tumor at pelvic sites, if treated with extended ®elds, the authors proposed to treat para-aortic nodes where there is a high probability of local control [14]. In the present survey, about 90% of the centers are treating this large volume if they have arguments for positive para-aortic and/or pelvic lymph nodes.…”

Section: Radiotherapymentioning

confidence: 95%

“…The EORTC trial performed on more advanced cervix cancer (comparing pelvic plus para-aortic vs. pelvic volume in early clinical stages with positive LAG or histologically proven pelvic nodes, and LACC, i.e. IIb and III), does not show any bene®t in survival, local control or overall distant metastases [14]. There was a clear increase in the incidence of severe digestive complications in patients receiving para-aortic irradiation (9 vs. 4.8%) [14,41].…”

Section: Radiotherapymentioning

confidence: 99%

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A survey on staging and treatment in uterine cervical carcinoma in the Radiotherapy Cooperative Group of the European Organization for Research and Treatment of Cancer

Coucke

Maingon

Ciernik

et al. 2000

Radiotherapy and Oncology

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Background: The treatment outcome of advanced stage uterine cervical carcinoma remains unsatisfactory. In order to elaborate a novel trial within The Radiotherapy Cooperative Group (RCG) of the European Organization for Research and Treatment of Cancer (EORTC), we conducted a survey in 1997±1998 to determine the variability of pre-treatment assessment and treatment options. The variability of choosing surgery, de®ned radiation therapy techniques and chemotherapy are investigated, as well as the center's choices of future treatment strategies.Methods: Fifty two of 81 RCG centers from the RCG have participated in the survey. As one would expect, there is a large variation in the techniques used for pretreatment evaluation and treatment options. There is no`standard' for reporting acute and late side effects. Chemotherapy is used neither systematically nor uniformly, and some centers continue to use neadjuvant chemotherapy modalities.Results: Furthermore, the survey reveals that there is a strong demand for the reduction of overall treatment-time, for clinical investigation of novel combined modality treatment strategies, especially chemo±radiation therapy, and also for the use of new radiation sensitizers.Conclusion: We conclude that a more homogeneous approach to the pretreatment evaluation as well as treatment techniques is required in order to allow adequate quality control in any future trial of the RCG in the EORTC. q

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Is Prophylactic Para-Aortic Irradiation Worthwhile in the Treatment of Advanced Cervical Carcinoma? Results of a Controlled Clinical Trial of the EORTC Radiotherapy Group

Cited by 13 publications

References 0 publications

Expression of anionic glutathione S transferase (GSTπ) gene in carcinomas of the uterine cervix and in normal cervices

Expression of anionic glutathione S transferase (GSTπ) gene in carcinomas of the uterine cervix and in normal cervices

Low podoplanin expression in pretreatment biopsy material predicts poor prognosis in advanced-stage squamous cell carcinoma of the uterine cervix treated by primary radiation

A survey on staging and treatment in uterine cervical carcinoma in the Radiotherapy Cooperative Group of the European Organization for Research and Treatment of Cancer

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