Time without symptoms and toxicity (TWIST) analysis of adjuvant radiation therapy for endometrial cancer.
OBJECTIVE
Postoperative radiotherapy in endometrial cancer reduces the risk of local relapse but is also associated with substantial acute and late reactions. The aim of our study was to evaluate time without tumor symptoms and toxicity (TWIST) in a consecutive series of 317 endometrial cancer patients administered postoperative irradiation.


METHODS
Both low-dose rate brachytherapy (BRT) and external beam irradiation (EBRT) were applied in 247 patients (78%), only BRT--in 49 (15%) and only EBRT--in 21 patients (7%). Median follow-up was 7.3 years (range, 4-21 years). TWIST analysis based on actuarial freedom from recurrent disease and from late radiotherapy effects was performed with the use of Kaplan-Meier method. The impact of patient- and treatment-related factors on TWIST was assessed with uni- and multivariate tests.


RESULTS
Five-year overall survival was 78%, and five-year disease free survival--75%. Recurrence occurred in 70 patients (22%), of whom in 11 (3.5%)--exclusively in the pelvis. Acute and late reactions of any grade occurred in 268 (85%) and 158 patients (51%), respectively. Late bowel effects of any grade were observed in 41% of patients. Severe late effects occurred in 35 patients (11%). Actuarial probability of two- and five-year survival free of disease and severe (grades 3 or 4) late effects (TWIST) was 84% and 71%, respectively (median TWIST, 16.2 years). When all-grade late effects were considered, two- and five-year TWIST probability was 50 and 30%, respectively, and median TWIST was only 2.0 years. When both acute and late reactions were taken into account, median TWIST was 22 months. In unifactorial test, higher age ( P = 0.013) FIGO stage ( P < 0.001) total radiotherapy dose ( P < 0.001) normalized total dose based on linear-quadratic model ( P = 0.001) EBRT fraction dose ( P < 0.001) and use of cesium BRT ( P = 0.042) were correlated with shorter TWIST. In multifactorial analysis, higher age ( P = 0.001) FIGO stage ( P = 0.001) and total radiotherapy dose ( P < 0.001) were independent factors correlated with shorter TWIST.


CONCLUSIONS
Endometrial cancer patients treated with postoperative irradiation have a long time interval without relapse and severe late toxicity. However, when any late normal tissue injury is considered, the median time without relapse and late toxicity is significantly shorter. The impact of mild late radiotherapy complications on the quality of life should be further investigated. TWIST calculation should be attempted in future prospective studies evaluating the role of postoperative radiotherapy.
Jereczek-Fossa
Barbara A
BA
Department of Radiation Oncology, European Institute of Oncology, 435 via Ripamonti, 20141 Milan, Italy.
Badzio
Andrzej
A
Jassem
Jacek
J
D000230:Adenocarcinoma / Q000532:radiotherapy* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001918:Brachytherapy; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000532:radiotherapy* / Q000601:surgery; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods; D012189:Retrospective Studies; D016019:Survival Analysis; D013997:Time Factors