Phase II Clinical Trial of Robotic Stereotactic Body Radiosurgery for Metastatic Gynecologic Malignancies

Abstract

Background: Recurrent gynecologic cancers are often difficult to manage without significant morbidity. We conducted a phase II study to assess the safety and the efficacy of ablative robotic stereotactic body radiosurgery (SBRT) in women with metastatic gynecologic cancers. Methods: A total of 50 patients with recurrent gynecologic cancer who had single or multiple (≤4) metastases underwent robotic-armed Cyberknife SBRT (24Gy/3 daily doses). Toxicities were graded prospectively by common toxicity criteria for adverse events (version 4.0). SBRT target responses were recorded following RECIST criteria (version 1.0). Rates of clinical benefit for SBRT and non-radiosurgical disease relapse were calculated. Disease-free and overall survivals were estimated by the Kaplan–Meier method and the Cox proportional hazards model was used to control for prognostic variables. Findings: SBRT was safely delivered, with 49 (98%) of 50 patients completing three prescribed fractions. The most frequent grade 2 or higher adverse events attributed to SBRT included fatigue (16%), nausea (8%), and diarrhea (4%). One (2%) grade four hyperbilirubinemia occurred. SBRT target response was 96% (48 of 50 patients). A 6-month clinical benefit was recorded in 34 [68% (95% CI, 53.2, 80.1)] patients. No SBRT targeted disease progressed. Non-radiosurgical disease relapse occurred in 31 (62%) patients. Median disease-free survival was 7.8 months (95% CI, 4.0, 11.6). Median overall survival was 20.2 months (95% CI, 10.9, 29.5). Interpretation: SBRT safely controlled metastatic gynecologic cancer targets. Given an observed high rate of non-radiosurgical disease relapse, a phase I trial assessing co-administration of SBRT and cytotoxic chemotherapy is underway. Funding: Case Comprehensive Cancer Center.

2-[18F]Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography Definition of Lung Targets in Vero Stereotactic Body Radiation Therapy Workflow

“…The selfreported incidence of pulmonary or chest-organ toxicity was very low in the 30-day period posttherapy. Reversible grade 2 or higher fatigue symptoms (20%) were in line with other SBRT trials (16%, [3]). Fatigue in the SBRT setting was attributed both to intense volumedirected radiation and to radiation-induced nuclear and mitochondrial DNA damage demanding excessive deoxynucleotide triphosphates, as considered before [20].…”

“…This notion was not new [1][2][3]. A prior observational study conducted in 27 patients suggested that a single 40% maximum standard uptake value benchmark sufficiently discriminated abdominopelvic SBRT clinical target volumes [1].…”

“…Because intracellular hexokinase traps 18 F-FDG as a sugar lookalike, PET has assisted in the spotting of and in the contouring of cancer targets for radiation treatment through image fusion, overlay, or side-by-side viewing [1][2][3][4]. As highly precise radiation delivery platforms become more mainstream, there has been a need for accurate anatomic and metabolic exactness of cancer targets [5].…”

Dynamic Lung Tumor Tracking for Stereotactic Ablative Body Radiation Therapy

“…Experience has led investigators to use ablative radiation against a variety of tumor types metastasizing to the lung 27,28 . The new SBRT platform introduces a radiation delivery system particularly attuned to the treatment of moving tumors.…”

Stereotactic body radiation therapy in head and neck, gynecologic, and pediatric malignancies

“…For purposes of discussion here, the subclass of stereotactic radiosurgery dealing with robotics [Cyberknife®, Accuray (Sunnyvale, CA, USA)] will be the focus given the preponderance of clinical data accumulated worldwide [27][28][29][30]. Robotic cyberknife stereotactic body radiosurgery for gynecologic cancers most commonly involves ablative dose (>8 Gy) delivery [34,35], over a 30-60-min irradiation time span, with sub-millimeter precision [36,37] and with motion tracking [38] all in an effort to avoid injury to normal abdominopelvic tissues. Paramount to the integration of robotic stereotactic body radiosurgery in clinical radiation oncology practice is better understanding of natural systems of DNA damage repair.…”