S. Kibudde1,2, M. Fahhoum3, S. E. Beltran Ponce4, V. Nankabirwa2, M. Nakalembe2, A. Kavuma5, P. Byakika2, W. Phipps6,7, J. Orem5, K. Beyer8, J. Zeng9, S. Mbulaiteye10, and S. Grover11; 1Uganda Cancer Institute, Uganda, Uganda, 2Makerere University, Kampala, Uganda, 3Medical College of Wisconsin Cancer Center, Milwaukee, WI, 4Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, 5Uganda Cancer Institute, Kampala, Uganda, 6University of Washington, Seatle, WA, 7Fred Hutch Cancer Center, Seatle, WA, 8Medical College of Wisconsin, Institute for Health and Equity, Milwaukee, WI, 9Department of Radiation Oncology, University of Washington - Fred Hutchinson Cancer Center, Seattle, WA, 10National Cancer Institute, Bethesda, MD, 11Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
Purpose/Objective(s): Cervical cancer is a significant health issue in low and middle-income countries (LMICs), with 604,127 new cases and 341,831 deaths annually. Despite this, access to treatment with radiotherapy (RT) in most LMICs is limited. Hypofractionated RT (HFRT) is the delivery of larger radiation doses (> 2.2Gy) per fraction over a shorter treatment duration. While HFRT improves patient compliance, data on its safety and efficacy in the treatment of cervical cancer are scarce. A systematic literature review was conducted to evaluate the safety and efficacy of HFRT in the treatment of cervical cancer.Materials/
Methods: A systematic search of published literature between January 1990 and December 2023 was performed on PubMed, African Index Medicus, LILACS, and MedNar. Studies describing the use of HFRT in curative treatment of cervical cancer were included. Using Rayyan, two independent reviewers blindly reviewed titles, and abstracts, for inclusion. Conflicts were resolved by a third independent reviewer. Lastly, full-length articles were reviewed. The analysis was based on RT dose per fraction, acute and late effects, tumour local control, and overall survival. Results: Fifty-two publications were screened, and 10 studies met the eligibility criteria. The majority (n =4) of studies were from Africa, followed by Asia (India, Bangladesh), and one study from Canada and the United Kingdom. The majority (n=8) were retrospective studies, and the most frequently studied regimen was 40Gy in 16 fractions. Acute RT toxicity was up to 61.7% with HFRT compared to 58% with CFRT, while late RT toxicity rates were between 11.3% - 42.6% with HFRT, compared to 12.8% with CFRT. Notably, HFRT regimens of >3Gy per fraction had higher later RT toxicity compared to 2.5Gy per fraction. There was no significant difference in acute and late effects of HFRT (40Gy in 16 fractions) compared to conventional fractionated RT (CFRT, 50Gy in 25 fractions). Concurrent chemotherapy was administered in 4 of the 10 studies, while brachytherapy was administered in 9 of the 10 studies. The average response rate at 6 months was 66.15% with HFRT compared to 69.98% with CFRT, while the average 5-year survival was 53.26% for HFRT compared to 53.8% for CFRT. HIV infection had a detrimental effect on local control and survival regardless of RT fractionation technique. Conclusion: HFRT has comparable outcomes and safety to CFRT in the treatment of cervical cancer. Higher radiation doses per fraction (>3Gy) were associated with increased acute and late toxicity rates. However, when comparing HFRT (40Gy in 16 fractions) to CFRT (50Gy in 25 fractions), there was no significant difference in terms of adverse effects. Further studies are warranted to prospectively evaluate the safety and efficacy of HFRT in the treatment of cervical cancer, with the ultimate goal of improving accessibility and outcomes in LMICs.
