Combined external and intracavitary irradiation in treatment of advanced cervical carcinomas: Predictive factors for local tumor control and early recurrences

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%.