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Combined external and intracavitary irradiation in treatment of advanced cervical carcinomas: predictive factors for local tumor control and early recurrences.
Orebro University Hospital.
Orebro University Hospital.
Radiation Physics, University Hospital, Örebro, Sweden.
Departments of Gynecological Oncology, University Hospital, Örebro, Sweden.
2010 (English)In: International Journal of Oncology, ISSN 1019-6439, Vol. 36, no 2, 371-8 p.Article in journal (Refereed) Published
Abstract [en]

In a series of 131 primary cervical carcinomas in FIGO stages I-IV suitable for combined external pelvic and intraluminal cervical-vaginal brachytherapy predictive and prognostic factors were analyzed with regard to locoregional tumor control, recurrences and survival data. Patients with prior surgery or patients treated with external beam therapy alone were excluded from this series. Concomitant chemotherapy was given to 47 patients (36%). The external beam therapy was given with a four-field technique (50-60 Gy) and brachytherapy with high dose-rate (Ir-192) using a ring applicator set. The dose (18-30 Gy) was specified according to the rules in ICRU 38 (a minimum dose to the surface of the target volume). Three or five fractions were given once a week in parallel with external beam irradiation. A CT-based 3-D dose-planning system (TMS) was used for the external beam therapy and for the brachytherapy planning (PLATO). The mean age of the patients was 65 years. One hundred and seven tumors were squamous cell carcinomas (82%) and 24 adenocarcinomas or adenosquamous carcinomas. One hundred and eight tumors were in FIGO stages I-II and 23 tumors in stages III-IV. The mean tumor diameter was 44 mm. Most tumors (92%) were moderately well or poorly differentiated. The primary cure rate of the complete series was 92% and 98% after chemoradiotherapy. Squamous cell carcinomas had complete remission in 96% and adenocarcinomas in 81% (Pearson Chi-square; P=0.00002). Tumor size was also highly significantly associated with local tumor control. The brachytherapy dose, the combined external and brachytherapy dose and the number of days of interruption (delay) of external irradiation were all significant predictive factors of local tumor control. In the complete series 39 recurrences (30%) were recorded. A lower FIGO stage, chemoradiotherapy, squamous cell histology, diploid DNA-profile, a higher brachytherapy dose, more brachytherapy fractions and a higher total combined irradiation dose were favorable factors with regard to the risk of tumor recurrences. The overall survival rate was 50% and the cancer-specific survival rate 65%. Tumor size was the strongest individual prognostic factor in multivariate analysis. Chemoradiotherapy therapy versus radiotherapy alone and squamous cell carcinomas versus adenocarcinomas were associated with improved survival rates. Early radiation reactions were recorded in 58% (mostly grade 1) and serious late radiation reactions (grade 3-4) in 11%.

Place, publisher, year, edition, pages
2010. Vol. 36, no 2, 371-8 p.
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:oru:diva-56897DOI: 10.3892/ijo_00000509ISI: 000273861900010PubMedID: 20043071Scopus ID: 2-s2.0-75449089521OAI: oai:DiVA.org:oru-56897DiVA: diva2:1085559
Available from: 2017-03-29 Created: 2017-03-29 Last updated: 2017-03-29Bibliographically approved
In thesis
1. Predictive and prognostic factors in cervical carcinomas treated with (chemo-) radiotherapy
Open this publication in new window or tab >>Predictive and prognostic factors in cervical carcinomas treated with (chemo-) radiotherapy
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A series of 131 women with cervical carcinoma FIGO stage I-IV were treated with external radiotherapy and intracavitary brachytherapy. In 47 patients (36%) concomitant chemotherapy was given. One hundred and twenty-one tumors (92%) achieved complete remission. Addition of chemotherapy increased primary cure rate to 98%. Tumor stage, tumor size, and histology were significant predictive factors for primary cure. Treatment related factors were: brachytherapy dose and interruption of irradiation.

Thirty-nine recurrences (30%) were recorded. Tumor stage, histology, and concomitant chemotherapy were significant predictive factors.

The 5-year cancer-specific survival rate of the complete series was 65%. Tumor size was a strong prognostic factor in multivariate analysis.

Serum samples from 44 patients were analyzed. Ten candidate biomarker proteins with regard to tumor recurrences were identified.

Five Hedgehog proteins were analyzed with immunohistochemistry. Residual tumor, local and distant recurrences and survival rate were associated with PTCH, SMO and GLI2. In the Wnt-β-catenin study intense staining of the membranes and nuclear staining > 5% were of significant predictive and prognostic value. Intense nuclear APC staining was associated with recurrences and cancer-specific survival rate.

Conclusion: Histology, tumor size and brachytherapy dose were important clinical predictive and prognostic factors. Multiprotein analysis identified ten biomarker proteins associated with tumor recurrences. Three proteins (PTCH, SMO, and GLI2) in the Hedgehog pathway were of predictive and prognostic value. In the Wnt-β-catenin pathway intensity of β-catenin membrane staining and accumulation in the nuclei as well as nuclear APC-expression were of predictive and prognostic value.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2017. 61 p.
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 159
Keyword
cervical carcinoma, radio-chemotherapy, biomarkers, predictive factors, prognostic factors, multiprotein analysis, Hedgehog pathway, Wnt/β-catenin pathway
National Category
Surgery
Research subject
Surgery
Identifiers
urn:nbn:se:oru:diva-56127 (URN)978-91-7529-185-7 (ISBN)
Public defence
2017-04-21, Örebro universitet, Campus USÖ, hörsal C1, Södra Grev Rosengatan 32, Örebro, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2017-03-06 Created: 2017-03-06 Last updated: 2017-04-19Bibliographically approved

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