Fractionation in medium dose rate brachytherapy of cancer of the cervix

Purpose: To establish an optimum fractionation for medium dose rate (MDR) brachytherapy from retrospective data of patients treated with different MDR schedules in comparison with a low dose rate (LDR) schedule. Methods and Materials: The study population consists of consecutive Stage IB-IIA-IIB patients who received radiotherapy alone with full dose brachytherapy plus external beam pelvic and parametrial irradiation from 1986-1993. Patients also receiving surgery or chemotherapy were excluded. The LDR group (n = 102, median follow-up: 80 months) received a median dose to Point A of two 32.5 Gy fractions at 0.44 Gy/h plus 18 Gy of external whole pelvic irradiation. The MDR1 group (n = 30, median follow-up: 45 months) received a mean dose of two 32 Gy fractions at 1.68 Gy/h. An individual dose reduction of 12.5% was planned for this group according to the Manchester experience, but only a 4.8% dose reduction was achieved. The MDR2 group (n = 10, median follow-up: 36 months) received a dose of two 24 Gy fractions at 1.65 Gy/h. The MDR3 group (n = 10, median follow-up 33 months) received a mean dose of three 15.3 Gy fractions at 1.64 Gy/h. And finally, the MDR4 group (n = 38, median follow-up: 24 months) received six 7.7 Gy fractions from two pulses 6 h apart in each of three insertions at 1.61 Gy/h. The median external pelvic dose to MDR schedules was between 12 and 20 Gy. The linear quadratic (LQ) formula was used to calculate the biologically effective dose (BED) to tumor (Gy(10)) and rectum (Gy(3)), assuming T1/2 for repair = 1.5 h. Results: The crude central recurrence rate was 6% for LDR (mean BED = 95.4 Gy(10)) and 10% for MDR4 (mean BED = 77.0 Gy(10)) (p = NS). The remaining MDR groups had no recurrences. Grade 2 and 3 rectal or bladder complications were 0% for LDR (rectal BED = 109 Gy(3)), 83% for MDR1 (BED = 206 Gy(3)), and 30% for MDR3 (BED = 127 Gy(3)). The MDR2 and MDR4 groups presented no complications (BED, 123 Gy(3), and 105 Gy(3), respectively). The LQ formula appears to correlate with late complications of the different MDR regimens. A BED above 125 Gy(3) was associated with Grade 2+3 rectal complications. Adequate central tumor control may be compromised with a tumor BED below 90-95 Gy(10). Conclusions: Medium dose rate brachytherapy at 1.6 Gy/h to Point A has a marked dose rate effect. Increased fractionation is the cost of overcoming the less favorable therapeutic ratio for MDR than for LDR. A larger (25%) reduction of brachytherapy dose than previously reported is also necessary. Our most recently developed schedule for Stage I-II patients is three insertions on three treatment days with six 8.0 Gy brachytherapy fractions, two on each treatment day, following or preceding an external whole pelvis dose of 18 Gy, and followed by additional external parametrial dose.