High Five (HiFi) Accelerated Partial Breast Irradiation Study

Sponsor

The Greater Poland Cancer Centre (Other)

Overall Status

Recruiting

CT.gov ID

NCT05142202

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To establish the role of adjuvant multicatheter interstitial high-dose-rate brachytherapy in doubly accelerated and radiobiologically equivalent irradiation scheme of 5 x 5,4 Gy in 3 days of treatment (High Five, HiFi-APBI) compared to the adopted long-term standard of APBI realized in 4-5 days (7-8 x 4-4,3 Gy) in selected women with breast low-risk invasive cancer or carcinoma in-situ, in terms of 3-month early and 2-year late toxicity.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Radiation: Breast Irradiation after Breast-Conserving Surgery	N/A

Detailed Description

Early low-risk breast cancer treatment with high-dose-rate brachytherapy (HDR-BT) (according to GEC-ESTRO, ASTRO, ABS recommendations) as a sole adjuvant treatment to the tumor bed after breast-conserving surgery (BCS) is acknowledged by prominent oncological societies in Poland and the world (PTB - Polish Brachytherapy Society, PTRO - Polish Society for Radiation Oncology, PTO - Polish Society of Oncology, ESTRO, ABS, ASTRO, ASCO). Treatment with multicatheter interstitial HDR-BT in the form of accelerated partial breast irradiation (APBI) was successfully verified in multi-institutional randomized clinical trials (Hungarian trial, GEC-ESTRO trial). It defined the currently widely used oncologically effective and clinically safe irradiation scheme of 8 x Gy in 5 days or 7 x 4,3 Gy in 4 days. In the USA, the irradiation scheme of 10 x 3,4 Gy is widely used in 5-10 days (e.g., NSABP-B39). Some European and American centers are investigating and publishing preliminary results of extremely shortened irradiation schemes of 4 x 6,25 Gy or 3 x 7,5 Gy in 2-3 treatment days, perioperatively (vAPBI trial - Valencia, TRIUMPH-T trial - Phoenix). In the Brachytherapy Department at Greater Poland Cancer Center (GPCC), the listed regimen of 7-8 x 4-4,3 Gy in 4-5 days has been used successfully since 2008. It results in very high local control rates and very low radiation-induced toxicity. APBI after BSC ensures, in properly selected low-risk patients, an equivalent local control rate and lower toxicity compared to whole breast irradiation with external beam radiation therapy (EBRT) The study hypothesis is that an additional moderately shortened irradiation scheme of 5 x 5,4 Gy in 3 consecutive days (two fractions daily with minimal 6 hours gap between fractions) does not increase early toxicity and 2-years late toxicity (primary endpoint). Also, it ensures the same or potentially higher 2-years local control probability compared to the standard regimen (control group).

What is essential, all the above-listed regimens are equivalent in terms of EQD2 calculations. The advantage of higher fraction doses that enable scheme shortening is relatively low radiobiological α/β ratio, estimated for breast cancer at around 4.

The study's primary goal is to prove the possibility of further gradual shortening of the total time of postoperative adjuvant treatment, thus, in the face of increasing breast cancer morbidity, increasing its accessibility. Indirectly, the shortened regimen may decrease the financial burden of the patient and the health system, reduce the patient's oncological treatment-related stress, absence from work, and separation from family. The project feasibility is likely since the only difference between standard and experimental procedures is in the dose and its number.

It's a prospective mono-institutional non-randomized open-label pilot study which results would be a base for further research on larger patients' groups in an anticipated multi-institutional randomized study.

The primary endpoint is to establish the role of adjuvant HDR brachytherapy in the allowable doubly accelerated and radiobiologically equivalent irradiation scheme of 5 x 5,4 Gy in 3 days of treatment (High Five, HiFi-APBI) compared to the adopted long-term standard of APBI realized in 4-5 days (7-8 x 4-4,3 Gy) in patients with breast low-risk invasive cancer or carcinoma in-situ, in terms of 3-month early and 2-year late toxicity.

Secondary endpoints: 1. Assessment of 2-years local control rate; 2. Review of 2-years cosmetic result; 3. Evaluation of the quality of life (QOL); 4. Evaluation of the overall survival (OS), disease-free survival (DFS), and distant metastases free survival (DFMS); 5. Analysis of the performed surgical approaches (tumorectomy, quadrantectomy, oncoplasty) preceding HDR-BT and their influence on the cosmetic results.

It is assumed to recruit a minimum of 60 participants in 2-3 years. The historical control group from the last three years counts over a hundred patients. The study is planned to be continued for up to 5 years to reach a substantially extended follow-up of 2 years.

Assumed causes of study termination: the occurrence of two or more cases of the treated area fat necrosis in which surgical intervention would be necessary (conservative treatment ineffective); too low recruitment (less than one-third of planned); occurrence of two or more similar and earlier not observed cases.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Doubly Accelerated Partial Breast Irradiation After Breast-Conserving Surgery for Early Breast Cancer - High Five (HiFi) APBI Study

Actual Study Start Date :

Oct 1, 2021

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Doubly Accelerated Partial Breast Irradiation after Breast-Conserving Surgery All recruited participants will be treated with adjuvant to breast-conserving surgery accelerated partial breast irradiation with multicatheter interstitial brachytherapy technique and prescribed five times 5,4 Gy delivered in 3 consecutive days (6 hours minimum gap between the fractions). Treatment starts not later than 12 weeks after surgery (optimally 4-8 weeks), after wound healing, and obtaining the final pathological report with full immunohistochemistry and proper risk group assignment. The control group consists of standard adjuvant APBI with multicatheter interstitial brachytherapy technique 8 x 4 Gy in 5 consecutive days or 7 x 4,3 Gy in 4 consecutive days (6 hours minimum gap between the fractions).	Radiation: Breast Irradiation after Breast-Conserving Surgery All recruited participants will be treated with adjuvant to breast-conserving surgery accelerated partial breast irradiation with multicatheter interstitial brachytherapy technique and prescribed five times 5,4 Gy delivered in 3 consecutive days (6 hours minimum gap between the fractions). Treatment starts not later than 12 weeks after surgery (optimally 4-8 weeks), after wound healing, and obtaining the final pathological report with full immunohistochemistry and proper risk group assignment.

Arm

Intervention/Treatment

Experimental: Doubly Accelerated Partial Breast Irradiation after Breast-Conserving Surgery

All recruited participants will be treated with adjuvant to breast-conserving surgery accelerated partial breast irradiation with multicatheter interstitial brachytherapy technique and prescribed five times 5,4 Gy delivered in 3 consecutive days (6 hours minimum gap between the fractions). Treatment starts not later than 12 weeks after surgery (optimally 4-8 weeks), after wound healing, and obtaining the final pathological report with full immunohistochemistry and proper risk group assignment. The control group consists of standard adjuvant APBI with multicatheter interstitial brachytherapy technique 8 x 4 Gy in 5 consecutive days or 7 x 4,3 Gy in 4 consecutive days (6 hours minimum gap between the fractions).

Radiation: Breast Irradiation after Breast-Conserving Surgery

Outcome Measures

Primary Outcome Measures

Adjuvant treatment - the early toxicity incidence [Up to 48 months]
The early toxicity incidence (radiodermatitis, hematoma, breast infection, intraoperative breast damage, breast pain) according to the Common Terminology Criteria for Adverse Events v5.0 (CTCAE) in 3 months frame.
Adjuvant treatment - the late toxicity incidence [up to 48 months]
The late toxicity incidence (skin, subcutaneous tissue) according to the RTOG/EORTC Late Radiation Morbidity Scoring Schema in 24 months frame.

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

stage 0-II breast cancer
Invasive ductal carcinoma (NOS, NST, other subtypes), invasive lobular carcinoma, ductal carcinoma in situ (DCIS)
Invasive carcinoma/DCIS, which is unifocal and unicentric
pT1-2, maximal tumor size < 3 cm
pN0 (no metastases to the nodes)
LVI(-) - no lymphovascular invasion
M0 (no distant metastases)
Surgical margins free of cancer (no tumor on ink) in each direction; in the case of DCIS, the minimum margin of 2 mm in each direction
Lack of indications to chemotherapy/immunotherapy pre- or postsurgically (e.g., triple-negative, HER2-positive breast cancer)
Treatment start not later than 12 weeks after surgery (optimally 4-8 weeks, after wound healing)
Informed handwritten signed patient's consent

Exclusion Criteria:

stage III-IV breast cancer
pT2-4, maximal tumor size ≥ 3 cm
surgical margins cannot be properly microscopically assessed
EIC(+) - presence of extensive intraductal component
Paget's disease or microscopically assessed skin involvement
pN1-3M1 (presence of nodal or distant metastases)
pre- or postsurgical indications for chemotherapy/immunotherapy
other cancer (less than five years at time of recruitment) except skin cancer or cured FIGO 0-I cervical cancer
time of pregnancy or lactation
collagen disorders (congenital or acquired)
psychiatric disorder disabling patient's compliance
breast appearance or postsurgical status disabling safe interstitial multicatheter implantation
lack of informed handwritten signed patient's consent