Hypofractionated Radiation Therapy in Patients With Breast Cancer (HRBC)

A Phase III Randomized Study Comparing Two Adjuvant Hypofractionated Radiation Schedules in Patients With Breast Cancer

The investigators at PGIMER have been practicing hypofractionation radiotherapy with a dose of 35Gy/15#/3wks to the chest wall in post mastectomy and 40Gy/16#/3wks in breast conservation in breast cancer patients for the last 4 decades. It is also a routine practice in UK and few centers in Canada. Hypofractionation reduces treatment time to half while maintaining cosmesis and gives control rates equal to conventional fractionation. As breast cancer is a leading cancer in females and radiation therapy is an important part of its local management, hypofractionation help the radiation centers worldwide to meet the growing need for radiation in breast cancer, particularly in developing countries where resources are limited. It also reduces the financial burden on the patient and family. In this study the investigators want to reduce the treatment duration from 3 weeks to 2 weeks. The study will include 1000 patients, 500 in each arm, with breast cancer post mastectomy or after breast conservative surgery to be treated with a radiotherapy dose of 34Gy in 10 fractions over 2 weeks in the study arm and 35Gy in 15 fractions over 3 weeks in the control arm. The primary endpoint of the study will be ipsilateral local tumour control. Secondary endpoints will be early and late adverse effects in normal tissues, quality of life, contralateral primary tumours, regional and distant metastases and survival.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Radiation: Hypofractionated Radiation therapy

Detailed Description

Patients to be included in this study will be pre-operatively staged according to American Joint Committee on Cancer (AJCC) 7th edition, International Union against cancer ( which uses TNM staging ) as stage I-III of breast carcinoma. Total 500 patients of histologically proven post lumpectomy/mastectomy cases of carcinoma breast suitable for radiotherapy will be enrolled in this study. Patients would be evaluated at the Department of Radiotherapy PGIMER, Chandigarh by doing a thorough clinical examination followed by routine investigations which will include hemogram, liver function tests, kidney function tests, chest X-ray. Patients will be treated by standard rectangular tangential fields.

• Study Type: Interventional
• Enrollment (Actual): 1070
• Phase: Phase 3

Contacts and Locations

Study Locations

• India
  • N/A = Not Applicable
    • Chandigarh, N/A = Not Applicable, India, 91 160012
      • Dr Budhi Singh Yadav

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Invasive carcinoma of the breast
• Breast conservation surgery or mastectomy
• Axillary staging &/or dissection
• Complete microscopic excision of primary tumour
• pT1-3 pN0-2 M0 disease
• Written informed consent
• Able to comply with follow up

Exclusion Criteria:

• Past history of malignancy except (i) basal cell skin cancer and CIN cervix uteri or (ii) non-breast malignancy allowed if treated with curative intent and at least 5 years disease free
• Contralateral breast cancer, including DCIS, irrespective of date of diagnosis
• Breast reconstruction using implants
• Concurrent cytotoxic chemotherapy (sequential neoadjuvant or adjuvant cytotoxic therapy allowed)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study; Patients with breast cancer post mastectomy or after breast conservative surgery to be treated with a hypofractionated radiotherapy dose of 34Gy in 10 fractions over 2 weeks.	Radiation: Hypofractionated Radiation therapy
Active Comparator: Control; Patients with breast cancer post mastectomy or after breast conservative surgery to be treated with a hypofractionated radiotherapy dose of 35Gy in 15 fractions over 3 weeks	Radiation: Hypofractionated Radiation therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local Recurrence	Any recurrence with in the irradiated area from completion of radiation	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute skin toxicity	Acute toxicity will be assessed using a RTOG grading system. Assessment will be carried out weekly during radiotherapy and for 4 weeks after treatment.	After 1 month of completion of radiation
Cosmetic assessment	done using Harvard/National Surgical Adjuvant Bowel and Breast Project(NSABP)/Radiation Therapy Oncology Group(RTOG) breast cosmesis grading scale. Grading will be done as Excellent- no or minimal difference between two breasts,Good- slight difference between two breasts,Good- slight and Fair minimal difference between two breasts, Fair- obvious difference between two breasts Poor- marked difference between two breasts. Excellent/good and fair/poor will be considered better and worse outcomes, respectively.	Baseline, 1 year, 3 years, 5 years
Quality of life	EORTC QLQ -30 The QLQ-C30 is composed of both multi-item scales and single-item measures, as well as five functional scales, three symptom scales, a global health status/QoL scale, and six single items.The scores must be averaged and linearly transformed to obtain a range of scores from 0 to 100, with a higher score representing a greater response level. Thus, a high score for a functional scale represents a healthy level of functioning and a high score for the global health status represents a high QoL, but a high score for the symptom scale represents a high level of symptomatology.	3 year, 5 year
Quality of life	EORTC QLQ-BR 23 It contains 23 items rated on a four-point scale ranging from 1 (not at all) to 4 (very much). The items assess the side effects of therapy, arm symptoms, breast symptoms, body image, and sexual function. Additionally, there are single items assessing sexual enjoyment, anxiety caused by hair loss, and future outlook. The scores range between 0-100 points. For scales evaluating function, a higher score represents a higher level of functioning. For scales evaluating symptoms, a higher score indicates more severe symptoms.	3 year, 5 year
Disease free survival	Time interval free from locoregional recurrence and metastasis	5 years, 10 years
Overall survival	From the date of diagnosis to death	5 years, 10 years
Arm edema	Will be graded by measuring arm circumference 10cm above and below the medial epicondyle of humerus. Treated side will be compared with the untreated opposite side as a reference. It will be classified as none, mild, moderate and marked if there was no difference, 0.5-2cm, 2.1-3cm and >3cm difference, respectively in the circumference of the affected and normal arm.	3 years, 5 years, 10 years
Late effects- pain, shoulder stiffness	A four point scale(none, a little, quite a bit, very much ) will be used to asess all late effects according to the RTOG LENT SOMA scale(Cox et al, 1995).	3 years, 5 years, 10 years
Late effects- Brachial plexopathy	If the patient had symptoms of pain in the arm, paresthesia, numbness, weakness, or other sensory symptoms then injury to the brachial plexus will be suspected and reported as brachial plexopathy.	3 years, 5 years, 10 years
Late effects- Lung, cardiac	Late lung and cardiac toxicity asess all late effects according to the RTOG LENT SOMA scale (Cox et al, 1995).	5 years, 10 years

Collaborators and Investigators

• Sponsor: Postgraduate Institute of Medical Education and Research
• Investigators: Principal Investigator: Budhi S Yadav, MD, PGIMER, Chandigarh, India

Publications and helpful links

General Publications

• Yadav BS. Accelerated partial breast irradiation. Radiother Oncol. 2009 Jan;90(1):161. doi: 10.1016/j.radonc.2007.10.005. Epub 2007 Oct 25. No abstract available.
• Yadav BS, Sharma SC, Patel FD, Ghoshal S, Kapoor RK. Second primary in the contralateral breast after treatment of breast cancer. Radiother Oncol. 2008 Feb;86(2):171-6. doi: 10.1016/j.radonc.2007.10.002. Epub 2007 Oct 24.
• Yadav BS, Sharma SC, George P, Bansal A. Post-mastectomy radiation beyond chest wall in patients with N1 breast cancer: is there a benefit? J Cancer Res Ther. 2014 Apr-Jun;10(2):279-83. doi: 10.4103/0973-1482.136560.
• Yadav BS, Sharma SC, Patel FD, Ghoshal S, Kapoor R, Kumar R. Nonbreast second malignancies after treatment of primary breast cancer. Int J Radiat Oncol Biol Phys. 2009 Apr 1;73(5):1489-92. doi: 10.1016/j.ijrobp.2008.07.004. Epub 2008 Sep 19.

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): December 1, 2020

Study Registration Dates

• First Submitted: October 26, 2015
• First Submitted That Met QC Criteria: August 29, 2019
• First Posted (Actual): August 30, 2019

Study Record Updates

• Last Update Posted (Actual): June 23, 2021
• Last Update Submitted That Met QC Criteria: June 22, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Breast cancer; hypofractionated radiotherapy; Hypofractionated radiation
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: HRBC