Accelerated Partial Breast Irradiation Using External Beam Volumetric Modulated Arc Therapy (VMAT): a Randomised Non-inferiority Trial of 30 Gy Versus 26 Gy in Five Fractions Investigating Patient-reported Outcomes (PUMA)

For women undergoing radiotherapy following surgery for early-stage breast cancer, breast-related quality of life (BrQoL) is an important consideration. Treating only the part of the breast by radiation where the cancer has been surgically removed (partial breast irradiation or "PBI") rather than the whole breast (whole breast irradiation) can reduce the toxic effects of radiotherapy. This trial aims to evaluate whether there is a difference in patient-reported BrQoL between two total doses of radiation given in five treatments using PBI. If BrQOL for the higher dose of PBI is no worse than the lower dose, using the higher dose would be advised as best practice, given that it is more likely to be more effective in reducing the chance of cancer coming back in the breast than the lower dose.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Radiation: Accelerated partial breast irradiation

Detailed Description

Single-blind, phase III, multisite, randomised non-inferiority trial. PBI will be planned and treated as per the protocol using VMAT. The prescribed dose will be 30 Gy in 5 daily fractions (Arm A) or 26 Gy in 5 daily fractions (Arm B). Participants will be blinded to their treatment allocation.

Follow-up will be at the following time points:

• Eight weeks following the end of radiation
• Every six months post-randomisation for two years following randomisation
• Three years post-randomisation (final visit)

Assessments to be conducted at each time point are:

• Clinical assessment
• Completion of Patient-Reported Outcome Measures (PROMs)
• Mammogram and ultrasound (baseline and annually)
• Documentation of IBTR - classified as a true recurrence or Elsewhere
• Documentation of any other type of recurrence (regional, distant, opposite breast)

Recruitment is planned for three years with a three-year follow-up period for all patients.

• Study Type: Interventional
• Enrollment (Estimated): 168
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: John Boyages, MB BS(Hons), FRANZCR, PhD, AM; Phone Number: +612 9480 4200; Email: John.Boyages@icon.team
• Study Contact Backup: Name: Nitika Neha, MSc (Biotchnology); Phone Number: +61 7 3737 4500; Email: research.iit@icon.team

Study Locations

• Australia
  • New South Wales
    • Wahroonga, New South Wales, Australia, 2076
      • Icon Cancer Centre Wahroonga
      • Contact: John Boyages, MBBS(Hons), FRANZCR, PhD; Phone Number: +612 9480 4200; Email: john.boyages@icon.team
  • South Australia
    • Windsor Gardens, South Australia, Australia, 5087
      • Icon Cancer Centre Windsor Gardens
      • Contact: Scott Curruthers, MBBS, FRANZCR; Phone Number: +61 8 8164 3600; Email: Scott.Carruthers@icon.team

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged greater than or equal to 50 years old
• Histologically confirmed Infiltrating ductal carcinoma (IDC) or pure DCIS, less than or equal to 20mm maximum size.
• Lobular carcinoma in situ (LCIS) is permitted.
• Histologic grade I or II
• Estrogen receptor (ER) +/- progesterone receptor (PR) positive in greater than or equal to 10% of cells and HER2 receptor-negative.
• Tumour bed identifiable on imaging via surgical clips
• Clear surgical margins
• Sentinel nodes negative (at least one node taken if invasive and no isolated tumour cells)
• No evidence of distant metastasis

Exclusion Criteria:

• Ink on surgical margins or positive histological margins
• Lymphatic vessel invasion (LVI)
• Bilateral breast cancer
• Invasive lobular carcinoma
• Pleomorphic LCIS
• Multifocal or multicentric invasive cancer
• Invasive carcinoma with associated DCIS greater than or equal to 30mm.
• Patients receiving neoadjuvant chemotherapy, anti-HER2 agents or endocrine therapy
• Patients receiving adjuvant chemotherapy or anti-HER2 agents.
• Previous Hodgkin's lymphoma requiring mantle radiation
• Prior radiation therapy to the ipsilateral breast
• Triple-negative breast cancer
• Documented mutation of BRCA1, BRCA2 or TP53, or at high genetic risk of breast cancer
• Known inflammatory conditions associated with higher complications after RT, such as active scleroderma, systemic lupus erythematosus (requiring steroids or immune suppressive therapy)
• Oncoplastic surgery where the primary tumour site is difficult to delineate
• No previous cancer (except BCC or SCC of the skin) unless in remission beyond five years of diagnosis
• People who are pregnant or planning to become pregnant
• People who are unable or unwilling to comply with protocol requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A: Hypofractionated PBI delivering a total dose of 30 Gy in five consecutive daily fractions.; PBI will be delivered using a VMAT planning and delivery technique. Prior to treatment patients are required to attend a treatment planning session that will assist with planning the treatment. The planning procedure will take up to approximately 60 minutes and involve a computed-tomography (CT) scan with the patient positioned in the treatment position. Treatment is expected to take around 15 minutes per treatment. The intervention will be prescribed by a radiation oncologist and administered by radiation therapists. During treatment, imaging will be completed to ensure treatment is administered accurately. All patients will complete breast cancer related quality of life questionnaires.	Radiation: Accelerated partial breast irradiation; Accelerated partial breast irradiation (APBI) will be delivered using Volumetric Modulated Arc Therapy (VMAT). Treatment will be started within 12 weeks of breast conserving surgery and within four weeks of randomisation. Treatment will occur in five (5) once-daily sessions and should be completed within seven (7) days of starting radiotherapy. Two total doses of APBI will be compared: 30 Gy and 26 Gy. The aim is to determine whether quality of life is no worse when a higher dose of APBI is used compared to a slightly lower dose of APBI. The results of this study will help to guide doctors choose the best dose of APBI for patients with early breast cancer in the future.
Active Comparator: Arm B: Hypofractionated PBI delivering a total dose of 26 Gy in five consecutive daily fractions.; The comparator for this study is another dose that is used as standard of care for APBI in Australia and globally. Planning and treatment procedures will be same as that for Arm A.	Radiation: Accelerated partial breast irradiation; Accelerated partial breast irradiation (APBI) will be delivered using Volumetric Modulated Arc Therapy (VMAT). Treatment will be started within 12 weeks of breast conserving surgery and within four weeks of randomisation. Treatment will occur in five (5) once-daily sessions and should be completed within seven (7) days of starting radiotherapy. Two total doses of APBI will be compared: 30 Gy and 26 Gy. The aim is to determine whether quality of life is no worse when a higher dose of APBI is used compared to a slightly lower dose of APBI. The results of this study will help to guide doctors choose the best dose of APBI for patients with early breast cancer in the future.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-reported breast-related cosmetic outcome,	Proportion of patients with a moderate or worse adverse cosmetic outcome, defined as a score of greater than or equal to 2.5 on the aesthetic sub-scale of the Breast Cancer Treatment Outcome Scale-12 (BCTOS-12).	36 months post randomisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-reported breast-related cosmetic outcome	BCTOS-12 aesthetic sub-scale scores	Baseline, 8 weeks post-treatment, 6, 12, 18, 24 and 36-months post randomisation.
Patient-reported breast-related functional outcome	BCTOS-12 functional sub-scale scores	Baseline, 8 weeks post-treatment, 6, 12, 18, 24 and 36-months post randomisation.
Patient-reported quality of life	BREAST-Q (V2.0) questionnaire scores for the following Breast Conserving Therapy (Post-operative) modules: - Physical well-being: chest - Satisfaction with breasts - Adverse effects of radiation - Fatigue - Impact on work	Baseline, 8 weeks post-treatment, 6, 12, 18, 24 and 36-months post randomisation.
Ipsilateral breast tumour recurrence (IBTR)	Cumulative incidence of local (true) recurrences of breast cancer within the index quadrant or newly diagnosed breast cancer within any other quadrant of the ipsilateral breast measured using results from standard of care imaging (mammogram, ultrasound, MRI).	Up to 36 months post-randomisation
Regional Recurrence	Cumulative incidence of any recurrence in the ipsilateral axillary, supraclavicular or internal mammary chain with or without recurrence in the breast or elsewhere measured using results from standard of care imaging (mammogram, ultrasound, MRI).	Up to 36 months post-randomisation
Locoregional disease recurrence	Cumulative incidence of IBTR plus any recurrence in the ipsilateral axillary, supraclavicular or internal mammary chain	Up to 36 months post-randomisation
Distant disease recurrence	Cumulative incidence of metastases to distant organs or bone sites measured using results from standard of care imaging (mammogram, ultrasound, MRI).	Upto 36 months post-randomisation
Patterns of care for treatment of disease recurrence (IBTR, locoregional, or metastatic)	Documented in patients' medical records	Upto 36 months post-randomisation
Patient satisfaction with treatment	Assessed qualitatively via an open-ended question: "Please write about your experience with breast cancer treatment, specifically focusing on your treatment with accelerated partial breast irradiation (APBI). Think about how you felt physically and emotionally and what the greatest challenges were during this time."	At 8-weeks and 12 months post-treatment.

Collaborators and Investigators

• Sponsor: Integrated Community Oncology Network
• Collaborators: Icon Cancer Foundation (ICF)
• Investigators: Study Chair: John Boyages, MB BS(Hons), FRANZCR, PhD, AM, Integrated Community Oncology Network

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): July 1, 2030
• Study Completion (Estimated): December 1, 2032

Study Registration Dates

• First Submitted: March 27, 2025
• First Submitted That Met QC Criteria: March 27, 2025
• First Posted (Actual): April 3, 2025

Study Record Updates

• Last Update Posted (Actual): April 3, 2025
• Last Update Submitted That Met QC Criteria: March 27, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Patient reported outcomes; Breast cancer; Partial breast irradiation (PBI)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 23.05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No