Accelerated Hyperfractionated Radiotherapy for Cervical Cancer: Multi-Institutional Prospective Study of Forum for Nuclear Cooperation in Asia Among Eight Asian Countries

Purpose

To evaluate the toxicity and efficacy of accelerated hyperfractionated radiotherapy (RT) for locally advanced cervical cancer.

Methods and Materials

A multi-institutional prospective single-arm study was conducted among eight Asian countries. Between 1999 and 2002, 120 patients (64 with Stage IIB and 56 with Stage IIIB) with squamous cell carcinoma of the cervix were treated with accelerated hyperfractionated RT. External beam RT consisted of 30 Gy to the whole pelvis, 1.5 Gy/fraction twice daily, followed by 20 Gy of pelvic RT with central shielding at a dose of 2-Gy fractions daily. A small bowel displacement device was used with the patient in the prone position. In addition to central shielding RT, intracavitary brachytherapy was started. Acute and late morbidities were graded according to the Radiation Therapy Oncology Group and Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria.

Results

The median overall treatment time was 35 days. The median follow-up time for surviving patients was 4.7 years. The 5-year pelvic control and overall survival rate for all patients was 84% and 70%, respectively. The 5-year pelvic control and overall survival rate was 78% and 69% for tumors ≥6 cm in diameter, respectively. No treatment-related death occurred. Grade 3-4 late toxicities of the small intestine, large intestine, and bladder were observed in 1, 1, and 2 patients, respectively. The 5-year actuarial rate of Grade 3-4 late toxicity at any site was 5%.

Conclusion

The results of our study have shown that accelerated hyperfractionated RT achieved sufficient pelvic control and survival without increasing severe toxicity. This treatment could be feasible in those Asian countries where chemoradiotherapy is not available.

Introduction

Cervical cancer is the second most common cancer in women worldwide (1). It is much more common in developing countries, where 83% of cases occur and where cervical cancer accounts for 15% of all female cancer cases (1). In 1993, we initiated a multi-institutional clinical study of radiotherapy (RT) alone with standard fractionation for Stage IIIB cervical cancer (CERVIX-I) among eight Asian countries, including China, Indonesia, Japan, Korea, Malaysia, Thailand, Philippines, and Vietnam. The 5-year overall survival rate for all 210 patients was 53% (2), similar to the rate reported in developed countries (3). However, it decreased to 31% in patients with tumors ≥6 cm in diameter, indicating the need for a more intensive strategy for locally advanced cases.

Altered fractionated RT has been one of the attempts to improve the therapeutic ratio in the hope of controlling locally advanced tumors by RT alone (4). Hyperfractionated RT permits dose escalation with a relatively decreased incidence of late complications, and accelerated fractionation aims to minimize tumor repopulation during treatment sessions by shortening the overall treatment time (OTT) (4). Accelerated hyperfractionated (AHF) RT combines the effects of hyperfractionation and accelerated fractionation with a decrease in the dose per fraction (i.e., by 1.5 Gy, twice-daily) and shortening of the OTT.

Because it was not possible to combine chemotherapy with RT in some participating institutes, we launched a clinical study of AHF RT to improve local control and survival. The purpose of this study was to evaluate the toxicity and efficacy of AHF RT in Asian women with locally advanced cervical cancer.