A Phase II Clinical Trial Design to Assess Intestinal Toxicity Reduction with Adaptive External Beam Radiation Therapy in the Treatment of Cervical Cancer (ARTIA-Cervix)
K Moore1*, X Ray2, D Branco3, C Mccann4, S Davidson5, L Levine6, K Russell7, S Kohlmyer8, J Mayadev9, (1) UC San Diego, La Jolla, CA, (2) UC San Diego, La Jolla, CA, (3) UC San Diego, La Jolla, CA, (4) Varian Medical Systems, ,,(5) Varian Medical Systems, ,,(6) Varian Medical Systems, ,,(7) Varian Medical Systems, ,,(8) ,Edmonds, WA, (9) UC San Diego, La Jolla, CA.
Presentations
TU-GH-BRB-2 (Tuesday, 7/12/2022) 1:45 PM - 3:45 PM [Eastern Time (GMT-4)]
Ballroom B
Purpose: To decrease acute high-grade gastrointestinal toxicity in external beam radiotherapy (EBRT) in gynecologic cancers, reducing large PTV margins safely with daily adaptive radiotherapy is proposed. ARTIA-Cervix is a single-arm prospective Phase II multi-institutional clinical trial to investigate the effect of adaptive radiotherapy for locally advanced cervical cancer in decreasing the rate of acute gastrointestinal toxicity. We report the rationale, primary objective, and feasibility of this clinical trial.
Methods: The primary objective is to demonstrate that gastrointestinal toxicity associated with adaptive pelvic IMRT (1.8Gy*25=45Gy) is lower than the observed rate for non-adaptive IMRT in node-negative gynecologic cancer (33% patient-reported toxicity on RTOG 1203), as measured by PRO-CTCAE (score≥3) at week 5 of EBRT. Using the Varian Ethos™ platform and ARTIA-Cervix protocol-specific autoplanning template, bowel V40Gy and V45Gy for 3-5mm PTV margins vs. current standard-of-care non-adaptive margins (7-15mm) were measured in 21 previously-treated node-negative cervical cancer patients. Time to complete the physicist-driven daily adaptive workflow was measured in 75 mock treatments (15 patients, 5 retrospective CBCTs each). Sample size and statistical power were calculated with the Wilson score interval, assuming 33%-20%=13% effect size for toxicity reduction.
Results: The pre-planning study showed bowel V40Gy and V45Gy reductions of 252cc->140cc and 167cc->43cc, respectively. Across three physicists and 75 separate sessions, the average time required to perform the daily adaptive workflow was 16.8 minutes (range:7-29 minutes). 106 subjects are sought as Wilson Score 95%-confidence interval for 25/106=23.6% is [16.5%,32.5%], implying null hypothesis of ≥33% toxicity incidence rate can be rejected at a 1-sided p<0.025 significance level if <25/106 subjects report PRO-CTCAE score >3. Power is 0.85 if true incidence rate is 20%.
Conclusion: The ARTIA-Cervix clinical trial will test the hypothesis that adaptive-enabled, reduced-margin cervical cancer radiotherapy reduces acute gastrointestinal toxicity. The study has multi-institutional IRB approval and will begin accrual in Spring 2022.
Funding Support, Disclosures, and Conflict of Interest: K Moore acknowledges consulting fees and honoraria from Varian Medical Systems. J Mayadev acknowledges consulting fees from Varian Medical Systems. X Ray acknowledges honoraria from Varian Medical Systems and a research agreement with Varian Medical Systems. Varian Medical Systems is the sponsor of this clinical trial.
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