Single vs Hypofractionated Irradiation For Timely Access to Partial Breast Radiotherapy

Radiation can be delivered in multiple fractions, or doses, and can take up to several weeks or months of treatment depending on the type of cancer. Radiation can also be offered in a single fraction. Both techniques have evidence for use in clinical care. Multiple fraction is offered to reduce the amount of radiation given at a single time that could reduce late toxicities. However, single fraction radiotherapy is more cost-effective and saves patient time. With this trial, we will compare single fraction vs. multiple fraction PBI in regards to their impact on quality of life, rates of provider and participant reported toxicities, and local control.

• Multiple Fraction PBI (Radiation): Participants randomized to Arm 1 will receive PBI with a dose of 26 Gy in 5 daily fractions.
• Single Fraction PBI (Radiation): Participants randomized to Arm 2 will receive PBI in a single fraction with a dose of 13 Gy.

Primary outcomes

• Number of participants accrued [2 years]: Number of participants who sign consent to be randomized to 1 vs 5 fractions of radiotherapy for PBI over a 2 year period

Secondary outcomes

• Time from CT simulation to plan approval [Baseline]: Measured as the time from the day of CT simulation to the date of plan approval.
• 2-Year Local Control Rates [6 weeks, 6 months, 12, months, 18 months, and 24 months post-treatment]: Absence of ipsilateral in-breast recurrence, defined as histologic evidence of invasive or in situ breast cancer in the ipsilateral breast 2 years post-treatment
• Quality of life assessed using the POSI-Breast questionnaire [Baseline, 6 weeks, 6 months, 12 months, 18 months, and 24 months post treatment]: Prospective Outcomes and Support Initiative (POSI) for Breast Data will be used to measure and compare the quality of life of participants in both arms.
• Rates of provider-rated toxicities: Occurrences of adverse events as measured by CTCAE [Baseline, 6 weeks, 6 months, 12 months, 18 months, and 24 months post treatment]: Participant-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Data will be used to measure and compare participant-reported toxicities in both arms.
• Participant-reported toxicities [Baseline, 6 weeks, 6 months, 12, months, 18 months, and 24 months post-treatment]: Occurrences of adverse events as measured by PRO-CTCAE
• Overall Survival (OS) [Approximately at the end of year 2 (study completion)]: Time from randomization to death from any cause, or last follow-up, whichever occurs first.
• Progression-Free Survival (PFS) [6 weeks, 6 months, 12 months, 18 months, and approximately at the end of 24 months]: Time from randomization to disease progression at any site, death, or last follow-up, whichever occurs first.

Sex: Female, ages: 40 Years to any

Inclusion Criteria:

* Female participants age 40 or older
* Able to provide informed consent
* pTis-2 pN0 cM0 breast cancer, with tumor size <3 cm as per provincial guidelines
* Able to complete electronic or paper entry of participant reported outcomes independently or with assistance from caregiver/family/friend/research staff
* Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
* A history and physical (clinical breast) examination, including ECOG performance status, performed within 8 weeks prior to enrollment.
* Participant is judged able to:

  * Maintain a stable position during therapy
  * Tolerate immobilization device(s) that may be required to deliver PBI safely
* Negative pregnancy test for People of Child-Bearing Potential (POCBP) within 4 weeks of RT start date

Exclusion Criteria:

* History of non-breast malignancies except adequately treated non-melanoma skin cancers, in situ cancers treated by local excision or other cancers curatively treated with no evidence of disease for ≥ 5 years.
* Uncontrolled concurrent malignant cancer
* Seroma not visible
* Ipsilateral implanted cardiac device
* Prior radiotherapy requiring summation for planning.
* Requirement for a radiation boost (as determined by the treating investigator)
* Positive surgical margins
* Surgical cavities lacking clear delineation (surgical clips are not required but may assist in target delineation)
* Known germline BRCA1/2 mutation.
* Serious medical comorbidities precluding radiotherapy (e.g., connective tissue disorders such as lupus or scleroderma)
* Pregnant or breastfeeding

• Results publication: Olson R, Cua M, Matthews Q, Laing J, Narinesingh D, Nichol A, Berrang T, Koulis T, Karan T, Chng N. Phase II single vs hypofractionated irradiation for timely access to partial breast radiotherapy (SHIFT-PB). BMC Cancer. 2025 Aug 8;25(1):1285. doi: 10.1186/s12885-025-14720-w. PMID 40781619

• Robert Olson, MD, MSc, FRCPC, Principal investigator, BC Cancer - Prince George