PRISM Trial: Partial Breast Versus Whole Breast Radiation in Early Breast Cancer

ClinicalTrials.gov ID

NCT07811635

Lead Sponsor

Jinnah Postgraduate Medical CentreOTHER_GOV

Overall Status

Not yet recruiting

Study Type

Interventional

Phase

Not Applicable

Enrollment

100Estimated

Last Update Posted

Sep 10, 2026Actual

Start Date

Sep 1, 2026Estimated

Primary Completion Date

Dec 31, 2026Estimated

Completion Date

Dec 31, 2027Estimated

Official Title

PRISM Trial: Partial Breast Versus Whole Breast Radiation in Ultra-Hypofractionated Irradiation; A Multicenter Study of Toxicity and DosiMetrics

Brief Summary

Breast-conserving surgery followed by radiotherapy is a standard treatment for women with early-stage breast cancer. Whole breast irradiation (WBI) is the current standard approach, but partial breast irradiation (PBI), which treats only the area surrounding the original tumor, may reduce radiation exposure to healthy tissues while maintaining similar treatment effectiveness.

The PRISM Trial is a prospective, multicenter, phase II randomized controlled trial that will compare ultra-hypofractionated PBI and WBI using the same radiation schedule of 26 Gy delivered in five fractions with intensity-modulated radiotherapy (IMRT). One hundred eligible women with early-stage breast cancer will be randomly assigned to receive either PBI or WBI after breast-conserving surgery.

The primary objective is to compare acute treatment-related skin toxicity between the two treatment approaches using both clinician-reported Common Terminology Criteria for Adverse Events (CTCAE v6.0) and patient-reported outcomes (PRO-CTCAE). Secondary objectives include evaluation of early and late toxicity, dosimetric parameters, normal tissue complication probability (NTCP), and the relationship between radiation dose distribution and clinical toxicity over 12 months of follow-up.

Detailed Description

Breast Cancer (BC) is the most common malignancy among women worldwide and represents a significant and growing health burden in Low- and Middle-Income Countries (LMICs), including Pakistan. According to GLOBOCAN (2022), approximately 2.3 million women were diagnosed with breast cancer globally, with nearly 670,000 deaths reported. Asia alone accounted for nearly 1 million new cases, representing 42.9% of the global burden.

Breast-Conserving Surgery (BCS) followed by Whole Breast Irradiation (WBI) remains the standard treatment for women with early-stage breast cancer. Recent advances in radiotherapy have demonstrated that ultra-hypofractionated WBI, delivered as 26 Gy in five fractions, provides comparable tumor control with reduced treatment duration and improved patient convenience. Partial Breast Irradiation (PBI) has also emerged as an attractive alternative by limiting radiation exposure to the tumor bed and surrounding tissues, thereby potentially reducing treatment-related toxicity while maintaining excellent oncologic outcomes in appropriately selected patients. Multiple randomized trials have demonstrated that PBI provides oncologic outcomes comparable to WBI in appropriately selected patients, with similar rates of ipsilateral breast tumor recurrence (IBTR). A meta-analysis of 14 randomized and observational studies involving over 17,000 patients reported comparable 5-year (RR 1.34) and 10-year (RR 1.29) IBTR rates between PBI and WBI, with reduced acute toxicity and similar late toxicity. The RAPID trial, a multi-center randomized study of 2,135 women, demonstrated non-inferior local recurrence rates at 8 years (3.0% vs. 2.8%) using PBI (38.5 Gy in 10 twice-daily fractions) compared with WBI; however, PBI was associated with significantly higher late toxicity and poorer cosmetic outcomes, with increased grade 1-2 toxicities and adverse cosmesis at 3 years. These findings were largely attributed to the twice-daily treatment schedule and shortened 6-hour interfraction interval, which may have limited normal tissue repair. This hypothesis was supported by evidence from head and neck radiotherapy demonstrating increased toxicity with shorter interfraction intervals. Subsequently, the Canadian phase II OPAR trial evaluated once-daily PBI (27.5 Gy or 30 Gy in 5 fractions) and demonstrated excellent cosmetic outcomes, low toxicity, and only three local recurrences at a median follow-up of 3.1 years, supporting once-daily PBI as a safer and more tolerable approach.

Further evidence from the IMPORT LOW trial (40 Gy in 15 fractions) and the Florence trial (30 Gy in 5 fractions delivered on alternate days) confirmed that appropriately delivered PBI achieves comparable local control to WBI while reducing acute and late toxicity and improving cosmetic outcomes. Similar findings have also been reported in the GEC-ESTRO and TARGIT-A trials, further supporting the oncologic safety of PBI in selected patients. In addition to reducing irradiated breast volume, PBI may decrease radiation exposure to critical organs such as the heart, potentially lowering the long-term risk of ischemic heart disease associated with WBI. Despite these encouraging results, important limitations remain, including heterogeneity in dose, fractionation, target delineation, and treatment techniques across studies, limited long-term follow-up for some PBI regimens, and the use of conventional rather than contemporary hypofractionated WBI as the comparator in many trials. Moreover, previous studies have primarily focused on local control and cosmesis, with limited evaluation of dosimetric parameters and their correlation with clinical outcomes, highlighting an important gap that warrants further investigation.

Furthermore, there is no prospective evidence directly comparing ultra-hypofractionated PBI and WBI using the same dose schedule and modern Intensity-Modulated Radiotherapy (IMRT) techniques. The PRISM trial aims to address this evidence gap by comparing toxicity, dosimetric parameters, and early oncologic outcomes between these two treatment approaches.

The primary objective of this study is to compare the incidence and severity of acute radiation-induced skin toxicity between patients receiving ultra-hypofractionated WBI and those receiving ultra-hypofractionated PBI.

Secondary objectives include comparing early late toxicity up to 12 months, evaluating dosimetric parameters, estimating Normal Tissue Complication Probability (NTCP), correlating dosimetric parameters with observed toxicity, and assessing intermediate oncologic outcomes including overall survival and breast cancer-specific survival.

• Breast Cancer Early Stage Breast Cancer (Stage 1-3)

• Ultra-Hypofractionated Partial Breast Irradiation
• Ultra-Hypofractionated Whole Breast Irradiation

Ages Eligible for Study

Adult (18-64)Older Adult (65+)

Sexes Eligible for Study

Female

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria:

• Women aged ≥45 years.
• Newly diagnosed, histologically confirmed breast carcinoma, including Invasive Ductal Carcinoma (IDC), Invasive Lobular Carcinoma (ILC), or Ductal Carcinoma in Situ (DCIS).
• Early-stage disease (T1-T2, node-negative [N0]), with no evidence of distant metastasis.
• Hormone receptor-positive disease (ER and/or PR positive).
• HER2-positive disease, provided patients have received or are receiving appropriate HER2-targeted therapy, as per institutional practice.
• Patients who have undergone breast-conserving surgery with no tumor on inked margins or no residual disease following re-excision.

Exclusion Criteria:

• Age <45 years.
• Multicentric disease.
• Locally advanced or node-positive disease (T3-T4 and/or N+) or evidence of distant metastasis.
• Lobular Carcinoma In Situ (LCIS).
• Triple-negative breast cancer.
• Positive surgical margins or incomplete breast-conserving surgery not suitable for re-excision.
• Prior ipsilateral breast irradiation.
• Non-breast malignancy within the past 5 years, except treated non-melanoma skin cancer or in-situ carcinoma.
• Pregnancy or lactation at enrollment.
• Inability to identify the tumor bed on planning Computed Tomography (CT), such as absence of surgical clips or seroma.
• Unacceptable radiotherapy planning feasibility for the experimental technique according to protocol constraints.

Primary Purpose

Treatment

Allocation

Randomized

Interventional Model

Parallel Assignment

Masking

Single

Lead Sponsor

Jinnah Postgraduate Medical CentreOTHER_GOV

nadeemp@yahoo.com+971505625860

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