Early clinical experience on inverse planned high dose rate interstitial brachytherapy in the treatment of locally advanced cervical cancer

Abstract

To report treatment outcomes of cervical cancer patients treated with external beam radiotherapy (EBRT) and inverse planned high dose rate (HDR) interstitial implants. Thirty-four patients with newly-diagnosed cervical cancer treated with inverse planned interstitial HDR brachytherapy between March 2001 and July 2003 were retrospectively reviewed. During this period, patients with locally advanced tumor extending beyond coverage of the intracavitary brachytherapy system and early stage disease with unfavorable anatomy were treated with interstitial HDR brachytherapy boost. Twenty-nine patients who were medically fit for chemoradiation were treated with a cisplatin-based regimen. Patients generally received 45 Gy to the whole pelvis and some received 50 Gy to the true pelvis. The median EBRT dose was 48 Gy (range 29–54 Gy). Brachytherapy was initiated during or shortly after the completion of EBRT. All implants were performed using a freehand transrectal ultrasound guided interstitial implant technique. All patients underwent CT based treatment planning and dwell time optimization using inverse planning simulated annealing (IPSA). HDR Iridium-192 brachytherapy was given in 2–5 fractions delivered in doses of 6.0 to 9.5 Gy per fraction using 1–2 implants, with an interfraction interval of at least 6 hours. The median overall treatment time was 47 days (range 31–112 days). Total radiation doses (TRDs) combining EBRT and HDR doses were calculated using biologically equivalent doses with a/b of 10 to convert to 1.8 Gy fractionation. The median TRD was 82 Gy (range 53–93 Gy). The local control rates (LC), rates of regional failure (RF) and distant metastases (DM), and disease-specific (DSS) and overall survival (OS) probabilities were calculated using the Kaplan-Meier method. Univariate analyses were performed using the log rank test to evaluate patient, tumor and treatment related factors. Multivariate analyses were performed using Cox proportional hazard model to identify independent predictors of outcome. The median follow up time was 14 months. The median age was 51 years old. AJCC Stage distribution was: Stage I (3), Stage II (5), Stage III (14), Stage IV (12). Eleven patients had N1 and 6 had M1 disease. The 2-year LC was 71%. The 2-year RF and DM were 12% and 18%, respectively. The 2-year DSS and OS were 77% and 61%, respectively. Multivariate analyses showed that age was a prognostic factor for local recurrence (p = 0.04). Chemotherapy (no vs. yes) and TRD (<85 vs. ≥ 85 Gy) were prognostic for overall survival (p = 0.02 and 0.04 respectively). For patients with TRDs ≥ 85 Gy, 1 out of 10 patients failed locally, whereas, 6 out of 24 patients who received < 85 Gy had local failures (p = 0.11). The only patient who failed after receiving ≥ 85 Gy completed her treatment over 112 days. There were two cases (6%) of grade 3 or 4 acute toxicities. One patient developed deep vein thrombosis and another patient developed a uterine abscess. One patient developed a fistula in the setting of local recurrence. No other grade 3 or 4 late toxicities have occurred. Analysis of the dose-volume histograms showed that the median target volume (TV) was 157 cc. With each fraction of HDR brachytherapy, the median % of TV receiving 90% of the prescribed dose (PD) was 95%. The median % of TV receiving 100% of the PD was 88%. The median % of TV receiving 150% of the PD was 43%. The median doses to 2 and 5 cc of the bladder were 6.2 and 5.4 Gy, respectively. The median doses to 2 and 5 cc of the rectum were 6.0 and 5.4 Gy, respectively. The median doses to 2 and 5 cc of the bowel were 4.8 and 4.4 Gy, respectively. The median dose to 0.1 cc of the urethra was 4.4 Gy. Interstitial HDR brachytherapy using a freehand technique and inverse planning is well tolerated with minimal acute and late complications. Although there was not a statistically significant difference for local failure, we recommend delivering combined EBRT and HDR doses of at least 85 Gy in 1.8 Gy fractionation for locally advanced cervical cancer