Meta-Analysis: Moderate Hypofractionation Improves Safety and Cosmesis Over Conventional Fractionation in Breast Cancer Radiotherapy
17 Sep, 2024 | 11:14h | UTCBackground:
Breast cancer remains the most prevalent malignancy among women worldwide, with postoperative radiation therapy playing a crucial role in reducing locoregional recurrence and improving survival outcomes. Conventional fractionation (CF), involving a total dose of approximately 50 Gy delivered over five to six weeks in daily fractions of 1.8–2 Gy, has been the historical standard. In recent years, hypofractionated regimens—including moderate hypofractionation (MHF) and ultra-hypofractionation (UHF)—have emerged as alternatives that offer shorter treatment durations. Despite evidence supporting hypofractionation, its adoption varies due to concerns about potential side effects, cosmetic outcomes, and the limited long-term data on UHF.
Objective:
To provide a comprehensive assessment of various radiation dose fractionation schemes—CF, MHF, and UHF—in breast cancer, focusing on side effects, cosmesis, quality of life, recurrence risks, and survival outcomes.
Methods:
A systematic review and meta-analysis were conducted by searching Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception to 23 October 2023. Randomized controlled trials comparing CF (daily fractions of 1.8–2 Gy over 5–6 weeks), MHF (fractions of 2.65–3.3 Gy over 3–5 weeks), and UHF (five fractions) were included. Two independent investigators screened studies, extracted data, and assessed risk of bias using the Cochrane Collaboration’s tool and the GRADE approach. Pooled risk ratios (RRs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. A network meta-analysis integrated all available evidence.
Results:
From 1,754 studies, 35 trials encompassing 20,237 patients were included. Compared with CF, MHF significantly reduced the risk of grade ≥2 acute radiation dermatitis:
- All patients: RR, 0.59; 95% CI, 0.51–0.69; P<0.001.
- Breast-Conserving Therapy: RR, 0.54; 95% CI, 0.49–0.61; P<0.001.
- Post-Mastectomy: RR, 0.68; 95% CI, 0.49–0.93; P=0.02.
MHF also showed lower incidences of:
- Hyperpigmentation: RR, 0.77; 95% CI, 0.62–0.95; P=0.02.
- Grade ≥2 Breast Shrinkage: RR, 0.92; 95% CI, 0.85–0.99; P=0.03.
MHF was associated with improved cosmesis and quality of life compared to CF. Survival and recurrence outcomes were similar across UHF, MHF, and CF regimens. While UHF demonstrated comparable safety and efficacy profiles, data were less conclusive due to fewer trials and shorter follow-up periods.
Conclusions:
Moderate hypofractionation improves safety profiles, cosmetic outcomes, and quality of life compared with conventional fractionation while maintaining equivalent oncological efficacy. Ultra-hypofractionation shows promise with similar short-term safety and effectiveness but requires further research for definitive conclusions.
Implications for Practice:
- Preferred Regimen: MHF should be considered the preferred radiation therapy regimen for breast cancer patients due to reduced side effects, improved cosmesis, shorter treatment duration, and maintained oncological outcomes.
- Ultra-Hypofractionation Potential: UHF offers advantages of further reduced treatment times and patient convenience but requires additional long-term data before widespread adoption.
- Resource Utilization: Adoption of hypofractionated regimens can improve healthcare resource utilization and enhance patient quality of life.
Study Strengths and Limitations:
Strengths include a comprehensive assessment of both clinical and patient-centered outcomes across a large number of randomized controlled trials, providing a multidimensional perspective crucial for informed clinical decision-making.
Limitations involve potential risk of bias due to lack of blinding in some studies, variability in outcome reporting across trials, and limited long-term data on UHF regimens.
Future Research:
Further studies are needed to solidify the evidence base for UHF, particularly regarding long-term safety and efficacy. Research should focus on optimizing fractionation regimens tailored to patient-specific factors, such as breast size and smoking status, to enhance outcomes.
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