Definitive External Beam Radiation Therapy With Stereotactic Body Radiation Therapy Boost for FIGO Stage IB-IIB Cancer of the Cervix: Minimum 4-Year Disease Control, Toxicity, and Quality of Life Outcomes from a Phase 2 Trial

Purpose/Objective(s): SBRT for gynecologic cancers may offer practical advantages over brachytherapy at similar radiobiologic dosing. Dose-fractionation SBRT schedules may be selected to approximate those of HDR, and SBRT eliminates the needs of optimal applicator placement and sedation. Herein, we report health-related quality of life (HRQOL), toxicity, and disease control outcomes of a prospective, phase II trial of SBRT for primary cervical cancers. Purpose/Objective(s): Eligible patients included those with (1) pathologically confirmed cervical squamous cell carcinoma or adenocarcinoma; (2) FIGO stage IB, IIA or IIB disease; (3) technical or medical contraindication to brachytherapy; and (4) primary GTV < 125 cc following induction therapy. Induction therapy consisted of external beam radiotherapy (EBRT) to a minimum dose of 45.0 Gy encompassing primary tumor and regional pelvic lymphatics. All patients received cisplatin-based chemotherapy concurrent to EBRT. SBRT boost treatment planning then followed, and GTV delineation was aided by co-registration of the boost planning CT set to a pre-EBRT FDG PET/CT scan and post-EBRT MRI. A boost dose of 40.0 Gy was prescribed to the primary tumor and delivered over a 10-day schedule of 5 fractions of 8.0 Gy each. Assessments included (1) disease response was determined pathologically by 3-month post-therapy biopsy and radiographically by biannual PET/CT imaging for 2 years; (2) acute and chronic toxicities were assessed using the National Cancer Institute's CTCAE v3 toxicity scales; and (3) quality-of-life was scored using FACT-G measurements. Results: Thirty-five patients with FIGO stage IB-IIB cervical cancer have been treated since June 2007 and have been followed for a median of 66.0 months and a minimum of 48.0 months. Stage distribution was as follows: 4/35 FIGO stage IB1, 9/35 FIGO stage IB2, 3/35 FIGO stage IIA1, 3/35 FIGO stage IIA2 and 16/35 FIGO stage IIB. Post-SBRT biopsy at 3 months was negative for 32 of 35 patients, or 91.4%, for all patients. At 5 years, estimated local control by combined pathologic and radiographic (i.e., PET SUVmax < 2.5) criteria at the SBRT treatment site is 88.5 % for all patients. No NCI CTCAE grade 3 or greater urinary or bowel toxicities have been observed to date. Post-treatment FACT-G scores were statistically superior compared to pre-treatment assessments for the following studied domains: physical, emotional, and functional well-being. Conclusion: At a minimum follow-up of 4 years, SBRT offers an effective and well-tolerated boost modality for selected FIGO stage IB-IIB cervix cancer patients otherwise contraindicated for brachytherapy. To our knowledge, this prospective phase 2 study reports the largest cohort of cervical cancer cases treated with curative intent using boost SBRT.