Main Session
Sep
28
SS 21 - Immuno-Radiotherapy and Liquid Biomarkers in Gynecologic Cancer: Toward Precision Care
214 - Personalized Ultra-Fractionated Stereotactic Adaptive Radiotherapy (PULSAR) Targeting the Cervical Primary in Stage IVB Cervical Cancer: Results of a Phase I Trial
Presenter(s)
Kevin Albuquerque, MD - Simmons Comprehensive Cancer Center, UTSW Radiation Oncology, Dallas, Texas
K. V. Albuquerque1, H. E. Grace2, M. Stein1, J. S. Lea3, R. D. Timmerman1, and C. R. Nwachukwu4; 1Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, 2Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, TX, 3Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, 4University of Texas Southwestern Department of Radiation Oncology, Dallas, TX
Purpose/Objective(s):
Standard-of-care (SOC) treatment for Stage IVB cervical cancer is combination platinum, taxol, and bevacizumab with the recent addition of pembrolizumab .The intensity and timing of systemic therapy (with the risk of synergistic toxicity with radiation) prevents timely administration of radiotherapy for these women and many patients with metastatic cervical cancer suffer morbidity from locoregional disease progression. PULSAR delivers ultra-fractionated radiation pulses over longer time intervals between each radiation treatment, allowing target adaptation based on tumor response. This is theorized to enhance immune activation and reduce toxicity by allowing for normal tissue repair and reduction in target volume according to tumor response. The purpose of this phase I trial was to evaluate the safety, pelvic toxicity, and local control of PULSAR delivered to the cervical primary in combination with SOC systemic therapy in patients with Stage IVB cervical cancer.Materials/Methods:
Eligible patients had ECOG status 0–3 with newly diagnosed IVB cervical cancer who were within a few weeks of initiating systemic therapy. No prior pelvic radiotherapy was permitted, except palliative doses =9 Gy PULSAR was delivered to the primary tumor at 8.5 Gy per pulse for up to five pulses (total 42.5Gy; BED=78.6) every 3–4 weeks, concurrent with SOC systemic therapy. MRI-based imaging was used for target and organ-at-risk delineation and a MR-Linac facilitated narrow margin adaptive treatment pulses. The primary endpoint was toxicity and secondary one was local control.Results:
Of the 12 enrolled patients, 9 received at least 3 pulses and were evaluable for toxicity. The median interval between systemic therapy and radiation pulses was 7 days (range 3–16). Median follow-up length was 16.3 months. Median progression-free survival was 14.3 months (95% CI 8.15 – not reached), and median overall survival was 18.5 months (95% CI 17.4 – not reached). Patterns of disease progression were assessed, including local pelvic versus distant progression. More than half of the patients (56%) had distant progression including 33% with distant-only recurrence. Only 1 patient (11%) had isolated local recurrence of the primary tumor. 3 patients (33%) remained free of progression at last follow-up. No dose-limiting toxicities were observed. Pelvic radiation–related toxicity was limited to grade 1 events, including diarrhea (n = 1) and dysuria (n = 1).Conclusion:
PULSAR delivered to the cervical primary concurrently with SOC systemic therapy is feasible and well tolerated in patients with Stage IVB cervical cancer, with minimal pelvic toxicity. These findings support further prospective evaluation of adaptive ultra-fractionated radiotherapy strategies to improve local disease management in the metastatic cervical cancer setting.