Stereotactic Body Radiation Therapy As A Boost Alternative For Nonmetastatic Cancer Of The Cervix And Endometrium: Disease Control And Quality Of Life Outcomes From A Phase 2 Trial At 3 Years' Minimum Follow-Up

Stereotactic body radiation therapy (SBRT) has been applied as a radioablative modality to multiple disease sites, achieving local control rates proximate to those observed following surgery. However, very little experience with SBRT in the management of gynecologic cancers has been reported to date. For patients contraindicated for brachytherapy or surgery, external beam radiation therapy alone offers historically poor disease control outcomes. To our knowledge, this prospective phase II study reports the largest cohort of endometrial and cervical cancer cases treated with curative intent using SBRT as a boost modality in place of brachytherapy. Protocol eligibility criteria included the following: (1) pathologically confirmed endometrial or cervical squamous cell carcinoma or adenocarcinoma (serous and clear cell histologies were excluded); (2) no radiographic evidence of extra-pelvic disease; (3) technical or medical contraindication to surgical therapy and brachytherapy; and (4) primary GTV volume less than 125 cm3. All patients first received external beam radiation therapy to a minimum dose of 45.0 Gy encompassing primary tumor and regional pelvic lymphatics. Boost SBRT treatment planning then followed, and GTV delineation was aided by coregistration of the boost planning CT set to a PET/CT scan and MRI. Prior to each SBRT fraction, target setup was verified by matching to organ-implanted radio-opaque fiducial markers and by assessing for deformations using cone beam CT imaging. A total radiation 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. Disease control response was assessed pathologically by 3-month post-therapy biopsy and radiographically by biannual PET/CT imaging. Acute and chronic toxicities were assessed using the National Cancer Institute's CTCAE v3 toxicity scales. Quality-of-life assessment was determined using FACT-G measurements. Forty-two patients with primary endometrial (n = 12) or cervical (n = 30) cancer have been treated since June 2007 and have been followed for a median of 62.0 months and a minimum of 36.0 months. Post-SBRT biopsy was negative for 35 of 42 patients, or 83.3% of all patients. At 5 years, estimated local disease control by pathologic and radiographic (i.e., SUVmax < 2.5) criteria at the SBRT treatment site is 78.6% for all patients and 88.2% for stages I – II patients. No grade 3 or greater urinary or bowel toxicities have been observed to date. Pre and post SBRT FACT-G scores were statistically similar in all studied domains: physical, social, emotional and functional well-being. At a median follow-up greater than 5 years and with a minimum follow-up of 3 years, SBRT appears to offer an effective and well-tolerated boost modality for the management of selected gynecologic cancer patients otherwise contraindicated for brachytherapy or surgery.