High-dose-rate intracavitary brachytherapy in locally advanced uterine cervix cancer using three different fractionation schedules: An Indian experience

Oral Presentations / Brachytherapy 8 (2009) 105e180 OR13 Presentation Time: 3:30 PM

GYN PROFERRED PAPERS I Sunday May 31, 2009 3:20 PMe4:30 AM OR12 Presentation Time: 3:20 PM A Comparison Between LDR and MRI Conformal HDR Brachytherapy of Cervical Cancer: Results, Patterns of Failure and Late Complications David L Bernshaw, MBBS, BMedSci, Sylvia van Dyk, DipSci, Chrishanthi I Rajasooriyar, MBBS, M.D., Kailash Narayan, MBBS, Ph.D., Srinivas Kondalsamy-Chennakesavan, MBBS, M.P.H. Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Purpose: This retrospective study of patients with locally advanced cervix cancer, compares patterns of failure, late toxicity and survival in patients treated for cure with chemoradiation then LDR or conformal image guided HDR (IGHDRc) brachytherapy (BT). IGHDRc planning uses real time trans-abdominal ultrasound (TAUS) and subsequent MRI imaging to: i) ensure and verify adequate and consistent uterine tandem placement, ii) localize target volume and define of normal tissue volumes and iii) provide adaptive conformal brachytherapy planning. Methods and Materials: Between Jan 1996-May 2006, 217 FIGO staged patients had initial MRI and PET and followup (including PET at 6 months). Post chemoRT, 90 patients received LDR BT (T & O, standard Pt A dose using Manchester loadings, TAUS for placement only and orthogonal planning films) and 127 received IGHDRc BT (MRI compatible T & O, TAUS for insertion, positioning and interfraction comparison and MRI.) A library plan is modified per TAUS parameters obtained using the tandem as fiducial marker. Post RT, MRI is obtained (applicator in situ), and the plan modified for subsequent fractions if needed. HDRc patients are prescribed 80 Gy (10) (EBRT plus BT) to the outer margin of the tumor target. Local control, survival and toxicity have been compared. Results: 5-year OS was 60% (SE 5 4%), 5-year FFS was 55% (SE 5 3%) (no sig. diff.). Local (central)/other pelvic failure was 9%/14% for both groups. Median time to recurrence was 6 months IGHDRc vs 7months LDR. IGHDRc mean Pt A dose was 11 Gy less than for the LDR plan. Local failure in patients receiving O72.6 Gy(10) to Pt A was 17.5% cf 3.1% if !72.6 Gy (10). Paraaortic/systemic failure is 21%/23% for the LDR group, 19%/23% for the IGHDRc group. Pt A, bladder and rectal point doses are lower cf traditional LDR plans. Gd 3/4 toxicity is 4% for the IGHDRc group reduced from 8% in the LDR group. 68% of the IGHDRc group are asymptomatic cf 42% of the LDR group. Conclusions: Compared with LDR, IGHDRc planning significantly reduces severe and symptomatic late radiation effects with similar patterns of failure and survival. Applicable in any setting, TAUS based IGHDRc has the potential to improve the therapeutic ratio but is likely to be of greatest utility for those treating cervix cancer with radiation in under-resourced settings where MRI is not available. Late Toxicity Rates/100 Person-years Followup by Types of Brachytherapy

RTOG Toxicity Gr

Rate/100 person-yrs FU HR LDR (95% HDRc CI)

Rate/100 person-yrs FU HR LDR (95% HDRc CI)

1

3.2 2.8

9.4 7.9

2

2.7 1.4

3&4

0.7 0.6

1.02 (0.412.54) 0.43 (0.141.27) 0.62 (0.094.09)

4.5 1.6 *

1.6 0.6

111

Rate/100 person-yrs FU HR LDR (95% HDRc CI)

0.67 13.4 10.8 (0.391.15) 0.33 12.9 3.4 * (0.110.94) * 0.38 4.6 1.7 * (0.072.08)

0.68 (0.411.13) 0.22 (0.110.46) * 0.33 (0.110.98) *

HR: Hazard Ratio HDRc relative to LDR. * 5 statistically significant

High-dose-rate intracavitary brachytherapy in locally advanced uterine cervix cancer using three different fractionation schedules: An Indian experience Sayan Kundu, MBBS, Swapnendu Basu, M.D., Koushik Ghosh, Aloke Ghosh Dastidar, M.D. Radiotherapy, Medical College & Hospital, Kolkata, West Bengal, India. Purpose: Carcinoma of the cervix is the most common malignancy among Indian women and most women present at an advanced stage. A combination of megavoltage external beam radiotherapy (EBRT) and intracavitary brachytherapy is the accepted definitive mode of treatment. The American Brachytherapy Society (ABS) has recommended that individual fraction size should be !7.5 Gy and range of fractions should be 4-8. The primary disadvantage of HDR brachytherapy is the potential late toxicity of large doses per fraction. Many HDR brachytherapy fractionation schedules, varying from institution to institution are in use and the optimal schedule is yet to be decided. To reduce the duration of hospital stay, to improve patient compliance and to decrease the patient load in our institution thereby treating more patients of cervical carcinoma by HDR-brachytherapy, we have undertaken this study to assess the feasibility of a large fraction size (9 Gy/# for 2 fractions) by HDRbrachytherapy in locally advanced carcinoma cervix. Study end points are local control, disease-free survival (DFS), acute and late radiation reactions. Methods and Materials: This is a single institution 3-arm prospective trial initiated in October 2004. A total of 149 patients with histologically proven squamous cell carcinoma of the cervix (Stage IIB-IIIB) with KPSO70 were enrolled in the study after informed consent. All the patients received external beam radiotherapy by four-field box technique to 50 Gy in 25 fractions over 5 weeks with concurrent chemotherapy (CDDP 40 mg/m2 weekly during EBRT). Arm 1 (n 5 49) patients received 4 fractions of HDR- intracavitary brachytherapy of 6 Gy/# each week. Arm 2 (n 5 51) patients were treated with 3 fractions of HDR intracavitary brachytherapy of 7 Gy/# each week and Arm 3 (n 5 51) patients were treated with 9 Gy/ # of HDR-brachytherapy for 2 fractions. After completion, patients are on 2 monthly followup to detect tumor response, recurrence (local or distant), acute and late reactions (recorded as per RTOG criteria). Results: Result of followup with a median duration of 36 months is presented here. The 3-year actuarial local control in Arm 1 was 71.42% (35/49 patients), in Arm 2 was 76.47% (39/51 patients) and in Arm 3 was 77.55% (38/49 patients) [p 5 0.42 compared to Arm 1 and 0.9 compared to Arm 2]. The local control according to stage was 89%, 67% and 63.5%, respectively, for stage IIB, IIIA and IIIB in Arm 1 in contrast to 87.5%, 73.5% and 69.25% in Arm 2 and 90.5%, 74.5% and 68% in Arm 3. Disease-free survival (DFS) rate at 3 years were 64.5%, 66.67% and 67.5% in Arm 1, Arm 2 and Arm 3, respectively. Two patients each in Arm 1 and Arm 2 developed grade 3 and 4 rectal toxicity. One patient in Arm 3 developed grade 3 rectal toxicity. Two patients in Arm 1 had Grade 3 bladder toxicity. One patient each in Arm 2 and 3 had >3 Grade bladder toxicity. Conclusions: High-dose-rate intracavitary brachytherapy (HDR-ICBT) using 9 Gy/fraction for 2 fractions one week apart is comparable to 7 Gy/ # for 3 fractions and 6 Gy/# for 4 fractions, in terms of local control and toxicity in locally advanced carcinoma cervix and can be standardized, provided a geometrically favored application is possible and dose to the critical structures minimized.

OR14 Presentation Time: 3:40 PM Comparison of CT and MRI cervical cancer brachytherapy target and normal tissue volumes Ramez N. Eskander, M.D.,1 Daniel J. Scanderbeg, Ph.D.,2 Cheryl Saenz, M.D.,1 Catheryn Yashar, M.D.2 1Reproductive Medicine, UCSD Medical Center, San Diego, CA; 2Radiation Oncology, UCSD, San Diego, CA. Purpose: To evaluate the differences between target and normal tissue delineation between MRI and CT in cervical cancer patients and to