Ultra-hypofractionated Radiotherapy in Breast Cancer Patients

Ultra-hypofractionated Adjuvant Radiotherapy After Breast Conserving Surgery in Breast Cancer Patients

The present multicenter, retrospective and prospective observational study, aims to evaluate an ultra-hypofractionated whole breast irradiation schedule (WBI, 26 Gy in 5 fractions), in order to confirm literature data (FAST-F study) in the clinical practice.

Patient population included women affected by early stage breast cancer (BC), both invasive and ductal carcinoma in situ, receiving ultra-hypofractionated WBI (with or without a tumor bed boost) after breast conserving surgery (BCS). Main exclusion criteria are mastectomy and regional nodal irradiation. Neoadjuvant and/or adjuvant systemic therapies are allowed. The primary otcome is acute and chronic toxicity evaluation. Secondary outcomes are: overall servival (OS), disease-free survival (DFS), rates of local and loco-regional recurrences, distant metastasis occurrence, cosmetic outcome and quality of life (QoL) assessment. Acute and late toxicities will be scored according to the Common Terminology Criteria for Adverse Events (CTCAE) scale version 5.0. Cosmetic assessment will be graded according to the Harvard scale. Frontal photographs of both breasts will be used to evaluate toxicity and cosmetic results. For QoL assessment the EORTC (European Organisation for Research and Treatment of Cancer), QLQ-C30 and EORTC-QLQ-BR23 questionnaires will be administered.

Study Overview

• Status: Recruiting
• Conditions: Female Breast Cancer
• Intervention / Treatment: Radiation: ultra-hypofractionated whole breast irradiation

Detailed Description

The present multicenter retrospective and prospective observational study aims to evaluate feasibility, toxicity, efficacy, cosmetic outcome and QoL in early stage BC patients treated with BC followed by ultra-hypofractionated WBI (with or without a tumor bed boost). This study was designed to confirm literature data (FAST-Forward trial) in the clinical practice ("real life"study). All enrolled patients will be treated with an ultra-hypofractionated WBI schedule (26 Gy delivered in 5 consecutive fractions, single dose 5.2 Gy), according to FAST-Forward trial. Whole breast irradiation should be followed or not by a tumor bed boost (sequential: 7.6 Gy in 2 consecutive fractions, single dose 3.8 Gy or simultaneous intergrated boost: 30 Gy in 5 consecutive fractions, single dose 6 Gy). Either three-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT) or helicoildal techniques are allowed. Breath control techniques may be used at the discretion of each partecipating centre. Main exclusion criteria are mastectomy and needs for regional nodal irradiation. Neoadjuvant and/or adjuvant systemic therapies are allowed.

The primary outcome of this study is acute and chronic toxicity evaluation. Secondary outcomes are: OS, DFS, rates of local and loco-regional recurrence, distant metastasis occurence, cosmetic outcome and QoL assessment. Acute and late toxicities will be scored according to the Common Terminology Criteria for Adverse Events (CTCAE) scale version 5.0 at each follow-up visit.

Regarding prospectively enrolled patient cosmetic assessment will be graded (by the physician and the patient) according to the Harvard scale and performed before the start of radiotherapy (RT), 6 months and 1, 2 and 5 years after the end of RT; frontal photographs of both breasts will be taken before the start of R, 6 months and 1, 2 and 5 years after the end of RT. In particular, two photographs will be taken of the patient's trunk region, one with the hands resting on the hips, the other with the arms raised above the head (avoiding patients face). Photographic documentation will be evaluated according to the consensus scoring method described by Haviland et al. For QoL assessment the EORTC (European Organisation for Research and Treatment of Cancer), QLQ-C30 and EORTC-QLQ-BR23 will be administered before the start of RT,1 month after the end of RT and then at 1, 2 and 5 years after the end of RT.

Follow-up visits are scheduled as follows: one month after the end of RT and then every 4-6 months for 5 years. Laboratory test (blood count, biochemical, with or without CEA and Ca15.3), mammography and breast ultrasound scans will be scheduled 4-6 months after the end of RT and then yearly. Additional exams will be prescribed during the follow up in order to detected any disease reccurence.

• Study Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

• Study Contact: Name: Cynthia Aristei, MD; Phone Number: +390755783254; Email: cynthia.aristei@unipg.it
• Study Contact Backup: Name: Isabella Palumbo, MD; Phone Number: +390755783254; Email: isabella.palumbo@unipg.it

Study Locations

• Italy
  • Perugia, Italy, 06132
    • Recruiting
    • Radiation Oncology Section, Department of Medicine and Surgery, University of Perugia
    • Principal Investigator: Cynthia Aristei, MD
    • Contact: Cynthia Aristei, MD; Phone Number: +390755783254; Email: cynthia.aristei@unipg.it
    • Contact: Isabella Palumbo, MD; Phone Number: +390755783254; Email: isabella.palumbo@unipg.it
    • Sub-Investigator: Isabella Palumbo, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Patients affected by early stage breast cancer (both invasive and ductal carcinoma in situ) receiving ultra-hypofractionated whole breast irradiation (with or without a tumor bed boost) after breast conserving surgery. Main exclusion critereria are mastectomy and regional nodal irradiation .Neoadjuvant and/or adjuvant systemic therapies are allowed.

Description

Inclusion Criteria:

• Female patients
• Age ≥ 18 years.
• Early stage breast cancer treated with breast conserving surgery
• Whole breast irradiation without regional nodal irradiation
• Infiltrating carcinomas
• CDIS
• Written informed consent

Exclusion Criteria:

• Age<18 years.
• Regional nodal radiotherapy.
• Distant metastases.
• Previous history of malignancy except basaloid skin tumours and CIN. Previous history of breast cancer is not an exclusion criteria if treated with curative intent and if patient is disease free at least 5 years from diagnosis.
• Presence of absolute radiotherapy contraindications (pregnancy, inability to maintain the correct treatment position) and relative radiotherapy contraindications (connective tissue diseases including rheumatoid arthritis, scleroderma, systemic lupus erythematosus, dermatomyositis and vasculitis, especially if the disease is in an active phase)
• Patient's refusal to use data for research purposes.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute toxicity	Evaluation of acute toxicity to confirm the results obtained in the prospective randomized FAST-Forward study. Acute toxicity will be scored according to the Common Terminology Criteria for Adverse Events (CTCAE) scale version 5.0	1-6 months after RT
Late toxicity	Evaluation of chronic late toxicity to confirm the results obtained in the prospective randomized FAST-Forward study. Late will be scored according to the Common Terminology Criteria for Adverse Events (CTCAE) scale version 5.0	from 6 months after RT to 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival	overall survival	1 month after RT and then every 4-6 months for 5 years
disease-free survival	disease-free survival	1 month after RT and then every 4-6 months for 5 years
rates of local and loco-regional recurrence	rates of local and loco-regional recurrence	1 month after RT and then every 4-6 months for 5 years
distant metastasis occurence	distant metastasis occurence	1 month after RT and then every 4-6 months for 5 years
cosmetic outcome	Breast cosmetic result will be graded according to Harvard scale of breast cosmesis (1. Excellent - 2. Good - 3. Fair - 4. Poor)	at baseline and then after 6 months and then 1, 2 and 5 years
QoL assessment	EORTC QLQ-C30	at baseline and then after 6 months and then 1, 2 and 5 years
QoL assessment	EORTC-QLQ-BR23	at baseline and then after 6 months and then 1, 2 and 5 years
photographic assessment	consensus scoring method described by Haviland et al.	at baseline and then after 6 months and then 1, 2 and 5 years

Collaborators and Investigators

• Sponsor: University Of Perugia
• Investigators: Principal Investigator: Cynthia Aristei, MD, Radiation Oncology Section, Department of Medicine and Surgery, University of Perugia

Publications and helpful links

General Publications

• Harris JR, Levene MB, Svensson G, Hellman S. Analysis of cosmetic results following primary radiation therapy for stages I and II carcinoma of the breast. Int J Radiat Oncol Biol Phys. 1979 Feb;5(2):257-61. doi: 10.1016/0360-3016(79)90729-6. No abstract available.
• Mariam NBG, Song YP, Joseph N, Hoskin P, Reeves K, Porta N, James N, Choudhury A. Hypofractionation: less is more? Oncotarget. 2021 Aug 17;12(17):1729-1733. doi: 10.18632/oncotarget.28023. eCollection 2021 Aug 17.
• Haviland JS, Ashton A, Broad B, Gothard L, Owen JR, Tait D, Sydenham MA, Yarnold JR, Bliss JM. Evaluation of a method for grading late photographic change in breast appearance after radiotherapy for early breast cancer. Clin Oncol (R Coll Radiol). 2008 Sep;20(7):497-501. doi: 10.1016/j.clon.2008.03.017. Epub 2008 May 27.

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2021
• Primary Completion (Anticipated): July 21, 2023
• Study Completion (Anticipated): July 21, 2026

Study Registration Dates

• First Submitted: October 5, 2022
• First Submitted That Met QC Criteria: October 16, 2022
• First Posted (Actual): October 19, 2022

Study Record Updates

• Last Update Posted (Actual): October 19, 2022
• Last Update Submitted That Met QC Criteria: October 16, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: breast conserving surgery; early stage breast cancer; ultra-hypofractionated whole breast irradiation
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: FAST-F-PG01

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