3734 - Quality Assurance Analysis of Staging and Radiotherapy in OUTBACK Trial: Impact of Protocol Permitted Variations on Clinical Outcomes in Locally Advanced Cervical Cancer
Presenter(s)
M. Y. Lin1, D. Luo2, E. Barnes3, S. Van Dyke4, Y. C. Lee5, K. Diamante5, C. Johnston6, W. Small Jr7, D. K. Gaffney8, P. Khaw9, A. Fyles10, S. M. Brooks11, J. S. Mayadev12, B. J. Monk13, K. Moore14, M. R. Stockler3, L. Mileshkin15, and K. Narayan16,17; 1Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia, 2NHMRC Clinical Trials Centre,The University of Sydney, Sydney, Australia, 3NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia, 4Department of Radiation Therapy Services, Peter Mac Callum Cancer Centre, Melbourne, Australia, 5NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia, 6Wellington Blood and Cancer Centre, Wellington Hospital, Wellington, New Zealand, 7Department of Radiation Oncology, Stritch School of Medicine, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL, 8Department of Radiation Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, 9Department of Radiation Oncology, Peter MacCallum Cancer Center, Melbourne, Australia, 10Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada, 11Auckland City Hospital, Auckland, New Zealand, 12GOG Foundation, Philadelphia, PA, 13University of Arizona College of Medicine Creighton University School of Medicine Phoenix, Phoenix, AZ, 14Fred & Pamela Buffett Cancer Center at the University of Nebraska, Omaha, NE, 15Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, Australia, 16Icon Cancer Centre, Melbourne, Australia, 17Department of Gynecology and Obstetrics, University of Melbourne, Melbourne, Australia
Purpose/Objective(s): The international randomized OUTBACK trial (ANZGOG 0902/RTOG 1174/NRG 0274) demonstrated that the addition of adjuvant chemotherapy after definitive chemoradiotherapy (CCRT) did not improve survival in locally advanced cervical cancer (LACC). This prespecified quality assurance analysis investigated whether protocol permitted variations in staging methods and radiotherapy techniques influenced clinical outcomes.
Materials/Methods: All participants underwent 3-dimensional conformal external beam radiotherapy(3D-CRT) with concurrent cisplatin and brachytherapy (BT), with extended field radiotherapy for common iliac nodal involvement. Patients were staged using FIGO 2008 clinically and radiologically. The variations examined included staging modality (CT/MRI versus PET/CT), parametrial and nodal boost usage and dose, BT prescription method [Point A versus High-risk Clinical Target Volume (HRCTV)], overall treatment time (OTT), and protocol compliance. Primary outcomes were pelvic control, locoregional recurrence, progressionfree survival (PFS), and overall survival (OS). Logistic regression was used for binary endpoints, Cox proportional hazards models for PFS and OS, and Fine-Gray competing risks regression for LRR.
Results: A complete radiotherapy dataset was available in 871 (95%) of 919 pts. Median followup was 60 months. Staging by PET-CT (n=560, 64.3%) vs CT/MRI (n=247, 28.4%) showed no association with pelvic control (OR 0.85, 95% CI 0.63-1.16, p=0.32), PFS (HR 0.93, 95% CI 0.72-1.20, p=0.58), or OS (HR 0.87, 95% CI 0.65-1.16, p=0.34). Staging modality was not associated with pelvic control, PFS, or OS. Parametrial or nodal boosts were used more commonly in higher stage and node-positive disease. Boost doses >5.4 Gy was associated with worse pelvic control in patients with node-positive 2008 FIGO stage I and II. No dose-response relationship was observed for nodal boosts for LRR or OS suggesting the presence of confounding factors. HR-CTV based BT prescription (n=123, 14.1%) used lower Point A doses (78.0±10.4 Gy, was associated with lower toxicity in comparison with Point A prescription (n=584, 67.0%). However, in node negative patients, pelvic control was similar in either prescription (p=0.7). OTT >56 days was associated with inferior OS (HR 1.41, 95% CI 1.06 ñ 1.86). and PFS (HR 1.30, 95% CI 1.02 to 1.65).
Conclusion: These results support the use of image guided brachytherapy and minimising prolonged treatment time. Staging modality was not associated with treatment outcomes. These support the use of robust, high-quality, pragmatic staging and chemoradiation to facilitate global participation in LACC trials
Keywords: Cervical cancer, quality assurance, radiotherapy, parametrial boost, nodal boost, brachytherapy, overall treatment time