Impact on treatment outcome and late effects of customized treatment planning in cervix carcinomas: baseline results to compare new strategies.
OBJECTIVE
The aim of the study was to determine the predictive factors of complications, to evaluate the impact of customized treatment planning on late normal tissue effects per stage, and to report disease-free survival (DFS) and local control (LC) rates.


METHODS
From 1970 to 1994, 642 patients were treated with radiotherapy alone for carcinoma of the intact uterine cervix. According to the International Federation of Gynecology and Obstetrics (FIGO) substaging, 34% were Stage I, 39% Stage II, and 27% Stage III. The analysis was divided into three periods: 1970-1978 (use of standard prescriptions),1979-1984 (implementation of individual adjustments), 1985-1994 (systematic individual adjustments). Five-year DFS, LC, and complications rates were calculated using the Kaplan-Meier method. Predictive factors of complications were determined by univariate analysis using frequency tables and nonparametric t-tests. Multivariate analysis consisted of a polychotomous stepwise regression.


RESULTS
The comparison of the three time periods showed a significant reduction of the external radiation dose (dose above 40 Gy in 47% of patients before 1979 vs. 36% after 1984), of the use of parametrial boost (55% vs. 39%), of the use of vaginal cylinder (28% vs. 11.5%), and of the HWT volume (combined intracavitary and external irradiation) (842 cc vs. 503 cc on average). The total sequelae/complications rate, all toxicity grades, all stages, all organs was 51%. Five-year actuarial rate per toxicity grade was: G1, 42%; G2, 23.5%; G3, 10%; G4, 3%. The three main predictive factors for rectal and bladder sequelae/complications (all toxicity grades) taking into account time period were: the increase of external radiation dose, the high dose rate at reference points, and the whole vagina brachytherapy. No G4 occurred in the third period. The rate of G3 complications dropped from 16% to 6% over time: from 5% during the first period to 0% during the third period in Stage I, from 8% to 6% in Stage II, and from 23% to 12% in Stage III. G3 currently describes a variety of clinical situations with a different impact on quality of life which justifies further refinements of definitions of late effects. In our experience the severity of G3 markedly decreased: less than one-third of G3 had a real impact on quality of life in the last period compared to more than two-thirds in the first period. Meanwhile, 5-year LC rates remained stable in Stages I and II, 91% and 85% respectively. Conversely they fell from 75% to 55% in Stage III, thus raising the problem of underdosage and/or more accurate staging with time.


CONCLUSIONS
Customized treatment planning eradicated lethal complications and provided a significant decrease of G3 in all stages while maintaining high cure rates in early stages. Dose reduction should be considered with caution in Stage III.
Department of Radiotherapy, Centre de Lutte Contre le Cancer Georges-François Leclerc, Dijon, France. ibarillot@dijon.fnclcc.fr
I
I
Barillot
J C
JC
Horiot
P
P
Maingon
G
G
Truc
G
G
Chaplain
J
J
Comte
J P
JP
Brenier
D000206:Actuarial Analysis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001918:Brachytherapy / Q000379:methods; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies; D011832:Radiation Injuries / Q000145:classification / Q000150:complications*; D011879:Radiotherapy Dosage; D012002:Rectal Diseases / Q000209:etiology; D012720:Severity of Illness Index; D016896:Treatment Outcome; D001745:Urinary Bladder Diseases / Q000209:etiology; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000532:radiotherapy*