Radiotherapy is one of the important methods of cancer treatment, but its duration often creates additional challenges for patients. A course of treatment may last several weeks and require daily visits, which can be particularly difficult for those who must travel long distances to reach a treatment center.
Over recent decades, reducing treatment duration while maintaining efficacy and safety has become an important focus in radiation oncology. Large-scale clinical trials have demonstrated that, for many patients with breast and prostate cancer, shorter courses of radiotherapy can provide disease control comparable to that achieved with conventional, longer treatment schedules.
These findings have significantly changed clinical practice. However, selecting a shorter treatment course still requires consideration of the specific diagnosis, the patient’s clinical condition, and potential adverse effects.
What Changes When the Duration of Radiotherapy Is Reduced?
Radiotherapy is delivered in individual treatment sessions known as fractions. With conventional fractionation, radiation is administered in relatively small doses over numerous sessions. Hypofractionation, by contrast, involves reducing the number of fractions while delivering a higher dose per session. The total prescribed dose is generally lower.
This approach is based on differences in the sensitivity of tumor and normal tissues to the dose delivered per fraction. In radiobiology, these differences are characterized using the alpha/beta (α/β) ratio, which helps assess the biological effects of different fractionation schedules.
Hypofractionation is divided into moderate and ultrahypofractionation. Moderate hypofractionation often involves treatment over 3-4 weeks, whereas ultrahypofractionation may require only 5-7 sessions. The choice of a particular schedule depends on tumor location, disease characteristics, and treatment objectives.
Breast Cancer: From Five Weeks of Treatment to One
The introduction of hypofractionation in breast cancer treatment occurred gradually. The UK START trials played an important role in this process, demonstrating that, for many patients, a conventional five-week course could be replaced with a three-week schedule without compromising treatment efficacy.
The START B trial compared two radiotherapy schedules: 40 Gy in 15 fractions and 50 Gy in 25 fractions. Long-term follow-up demonstrated that the three-week course was non-inferior to the five-week course in terms of disease control, while the incidence of certain late adverse effects was lower. These findings contributed to the establishment of moderate hypofractionation in breast cancer treatment.
The next important step was the phase III FAST-Forward trial, which evaluated whether the duration of radiotherapy could be reduced from three weeks to one. Three treatment schedules were compared: 40 Gy in 15 fractions, 26 Gy in 5 fractions, and 27 Gy in 5 fractions.
Five-year follow-up results demonstrated that the five-fraction schedule was non-inferior to the three-week course in terms of local control. The ten-year results published in 2026 further confirmed the efficacy of the one-week treatment schedule. Over ten years, tumor recurrence in the treated breast occurred in 2.1% of patients in the 26 Gy group, compared with 3.6% in the 40 Gy group. Despite this numerical difference, the findings do not establish the superiority of the one-week course, but they support its non-inferior efficacy.
An important difference was also observed between the two five-fraction schedules. Late adverse effects were more frequent in the 27 Gy group than in the 26 Gy group. These included breast tissue induration (fibrosis) and changes in breast shape. The findings demonstrate that, when high doses per fraction are used, even relatively small differences in total dose may affect treatment safety.
Some questions remain regarding the use of five-fraction schedules for regional lymph node irradiation. The corresponding FAST-Forward substudy reported promising results. However, the relatively small number of participants and limited long-term follow-up data do not yet allow a comprehensive assessment of late adverse effects.
Radiotherapy following mastectomy and breast reconstruction also warrants separate consideration. One of the main concerns in this setting is whether hypofractionation increases the risk of reconstruction-related complications, including capsular contracture, changes in breast shape, and the need for implant removal.
The phase III RT CHARM trial was conducted to investigate this question and included 898 patients. Two treatment schedules were compared: 42.56 Gy in 16 fractions and 50 Gy in 25 fractions. During the two-year follow-up period, reconstruction-related complications occurred in 12.3% of patients in the three-week treatment group and 10.2% in the five-week group. The study demonstrated that the three-week schedule was non-inferior to the five-week schedule regarding the risk of complications. These findings support the use of moderate hypofractionation following breast reconstruction, although the risk of complications cannot be completely eliminated.
Prostate Cancer: From Eight Weeks to Five Sessions
Hypofractionation has also become an important component of prostate cancer treatment. Its use is supported by both radiobiological evidence and the results of large-scale clinical trials.
The CHHiP trial compared a conventional 37-fraction course with shorter treatment schedules. The results demonstrated that 60 Gy in 20 fractions was non-inferior to conventional treatment in terms of disease control. The incidence of late adverse effects was also similar during long-term follow-up. This study played an important role in establishing moderate hypofractionation as a standard treatment option for prostate cancer.
The HYPO-RT-PC trial evaluated ultrahypofractionation in patients with intermediate and high-risk localized prostate cancer. Two schedules were compared: 42.7 Gy in 7 fractions and 78 Gy in 39 fractions. The seven-fraction course demonstrated non-inferior efficacy compared with conventional treatment in terms of disease control. However, when interpreting these results, it is important to consider that radiotherapy was delivered predominantly using three-dimensional conformal radiotherapy (3D-CRT), and patients did not receive androgen deprivation therapy.
The PACE-B trial is particularly noteworthy, as it evaluated the efficacy of five-fraction stereotactic body radiotherapy (SBRT) in men with low- and intermediate-risk localized prostate cancer.
At five years, 95.8% of patients treated with SBRT remained free from biochemical or clinical progression, compared with 94.6% in the conventional or moderately hypofractionated radiotherapy group. The trial confirmed the non-inferior efficacy of five-fraction SBRT in terms of disease control.
However, the incidence of late genitourinary adverse effects was higher in the SBRT group. Over the five-year follow-up period, grade 2 or higher adverse effects occurred in 26.9% of patients in the SBRT group, compared with 18.3% in the comparator group. Therefore, assessment of baseline urinary function and potential complications is particularly important when selecting this treatment schedule.
On October 27, 2026, updated clinical practice guidelines from the American Society for Radiation Oncology (ASTRO) were published in Practical Radiation Oncology, replacing the 2018 guidelines. According to the updated recommendations, moderate hypofractionation is preferred over conventional fractionation across all risk groups of localized prostate cancer. Five-fraction SBRT is considered a standard treatment option for patients with low- and intermediate-risk disease, while its use in high-risk patients may be considered in selected cases following individualized assessment.
Why Is This Issue Important for Georgia?
Wider implementation of hypofractionation in Georgia could provide significant benefits for both patients and the healthcare system. Reducing treatment duration is particularly important for patients who must travel to another city to receive radiotherapy. Shorter treatment courses reduce travel and accommodation expenses, decrease the number of days missed from work, and make it easier for patients to integrate treatment into their daily lives.
For healthcare institutions, reducing the number of treatment sessions creates opportunities for more efficient use of radiotherapy equipment. This may allow more patients to receive treatment within the same period and reduce waiting times before radiotherapy begins.
However, the implementation of hypofractionation should not be driven solely by savings in time and costs. Treatment efficacy and safety must remain the priorities, requiring appropriate technical capabilities, qualified personnel, and adequate quality assurance.
For Georgia, it is important to evaluate current clinical practice, including which hypofractionated schedules are being used, for which diagnoses, and on the basis of which clinical guidelines. Reliable local data would support the further implementation of this approach and improve access to treatment.
Hypofractionation – Opportunities and Limitations
Hypofractionation has significantly changed radiotherapy practice in breast and prostate cancer. Clinical trials confirm that, in appropriately selected patients, treatment duration can be reduced without compromising efficacy.
However, a shorter treatment course is not the optimal choice for every patient. Selection of a treatment schedule must take into account disease characteristics, the patient’s clinical condition, and potential adverse effects. Particularly when higher doses per fraction are used, precise treatment planning, image guidance, and appropriate technical capabilities are essential.
The main advantage of hypofractionation is not simply reducing the number of treatment sessions. Its goal is to provide evidence-based, effective, and safe treatment tailored to the needs of each individual patient.
Author: Mariam Pkhaladze, MD, Radiation Oncology Resident
