Comparing treatment uncertainty for ultra- vs. standard-hypofractionated breast radiation therapy based on in-vivo dosimetry

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Abstract

Background and purpose

Postoperative ultrahypofractionated radiation therapy (UHFRT) in 5 fractions (fx) for breast cancer patients is as effective and safe as conventionally hypofractionated RT (HFRT) in 15 fx, liberating time for higher-level daily online Image-Guided Radiation Therapy (IGRT) corrections. In this retrospective study, treatment uncertainties occurring in patients treated with 5fx (5fx-group) were evaluated using electronic portal imaging device (EPID)-based in-vivo dosimetry (EIVD) and compared with the results from patients treated with conventionally HFRT (15fx-group) to validate the new technique and to evaluate if the shorter treatment schedule could have a positive effect on the treatment uncertainties.

Materials and methods

EPID-based integrated transit dose images were acquired for each treatment fraction in the 5fx-group (203 patients) and on the first 3 days of treatment and weekly thereafter in the 15fx-group (203 patients). A total of 1015 EIVD measurements in the 5fx-group and 1144 in the 15fx-group were acquired. Of the latter group, 755 had been treated with online IGRT correction (i.e., Online-IGRT 15fx-group).

Results

In the 15fx-group 12.0% of fractions failed (FFs) compared to 3.8% in the 5fx-group and 6.9% in the online-IGRT 15fx-group. Causes for FFs in the 15fx-group compared with the 5fx-group were patient positioning (7.4% vs. 2.2%), technical issues (3.1% vs. 1.2%) and breast swelling (1.4% vs. 0.5%). In the online-IGRT 15fx-group, 2.5% were attributed to patient positioning, 3.8% to technical issues and 0.5% to breast swelling.

Conclusions

EIVD demonstrated that UHFRT for breast cancer results in less FFs compared to standard HFRT. A large proportion of this decrease could be explained by using daily online IGRT.

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Most cited references 34

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Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial

Adrian Murray Brunt, Joanne Haviland, Duncan Wheatley … (2020)

Summary Background We aimed to identify a five-fraction schedule of adjuvant radiotherapy (radiation therapy) delivered in 1 week that is non-inferior in terms of local cancer control and is as safe as an international standard 15-fraction regimen after primary surgery for early breast cancer. Here, we present 5-year results of the FAST-Forward trial. Methods FAST-Forward is a multicentre, phase 3, randomised, non-inferiority trial done at 97 hospitals (47 radiotherapy centres and 50 referring hospitals) in the UK. Patients aged at least 18 years with invasive carcinoma of the breast (pT1–3, pN0–1, M0) after breast conservation surgery or mastectomy were eligible. We randomly allocated patients to either 40 Gy in 15 fractions (over 3 weeks), 27 Gy in five fractions (over 1 week), or 26 Gy in five fractions (over 1 week) to the whole breast or chest wall. Allocation was not masked because of the nature of the intervention. The primary endpoint was ipsilateral breast tumour relapse; assuming a 2% 5-year incidence for 40 Gy, non-inferiority was predefined as ≤1·6% excess for five-fraction schedules (critical hazard ratio [HR] of 1·81). Normal tissue effects were assessed by clinicians, patients, and from photographs. This trial is registered at isrctn.com, ISRCTN19906132. Findings Between Nov 24, 2011, and June 19, 2014, we recruited and obtained consent from 4096 patients from 97 UK centres, of whom 1361 were assigned to the 40 Gy schedule, 1367 to the 27 Gy schedule, and 1368 to the 26 Gy schedule. At a median follow-up of 71·5 months (IQR 71·3 to 71·7), the primary endpoint event occurred in 79 patients (31 in the 40 Gy group, 27 in the 27 Gy group, and 21 in the 26 Gy group); HRs versus 40 Gy in 15 fractions were 0·86 (95% CI 0·51 to 1·44) for 27 Gy in five fractions and 0·67 (0·38 to 1·16) for 26 Gy in five fractions. 5-year incidence of ipsilateral breast tumour relapse after 40 Gy was 2·1% (1·4 to 3·1); estimated absolute differences versus 40 Gy in 15 fractions were −0·3% (−1·0 to 0·9) for 27 Gy in five fractions (probability of incorrectly accepting an inferior five-fraction schedule: p=0·0022 vs 40 Gy in 15 fractions) and −0·7% (−1·3 to 0·3) for 26 Gy in five fractions (p=0·00019 vs 40 Gy in 15 fractions). At 5 years, any moderate or marked clinician-assessed normal tissue effects in the breast or chest wall was reported for 98 of 986 (9·9%) 40 Gy patients, 155 (15·4%) of 1005 27 Gy patients, and 121 of 1020 (11·9%) 26 Gy patients. Across all clinician assessments from 1–5 years, odds ratios versus 40 Gy in 15 fractions were 1·55 (95% CI 1·32 to 1·83, p<0·0001) for 27 Gy in five fractions and 1·12 (0·94 to 1·34, p=0·20) for 26 Gy in five fractions. Patient and photographic assessments showed higher normal tissue effect risk for 27 Gy versus 40 Gy but not for 26 Gy versus 40 Gy. Interpretation 26 Gy in five fractions over 1 week is non-inferior to the standard of 40 Gy in 15 fractions over 3 weeks for local tumour control, and is as safe in terms of normal tissue effects up to 5 years for patients prescribed adjuvant local radiotherapy after primary surgery for early-stage breast cancer. Funding National Institute for Health Research Health Technology Assessment Programme.

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Innovations in image-guided radiotherapy.

Guy Storme, Mark de Souza, Nadine Linthout … (2007)

The limited ability to control for the location of a tumour compromises the accuracy with which radiation can be delivered to tumour-bearing tissue. The resultant requirement for larger treatment volumes to accommodate target uncertainty restricts the radiation dose because more surrounding normal tissue is exposed. With image-guided radiotherapy (IGRT) these volumes can be optimized and tumoricidal doses can be delivered, achieving maximal tumour control with minimal complications. Moreover, with the ability of high-precision dose delivery and real-time knowledge of the target volume location, IGRT has initiated the exploration of new indications for radiotherapy, some of which were previously considered infeasible.

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Ten-Year Results of FAST: A Randomized Controlled Trial of 5-Fraction Whole-Breast Radiotherapy for Early Breast Cancer

Adrian Murray Brunt, Joanne Haviland, Mark Sydenham … (2020)

PURPOSE Previous studies of hypofractionated adjuvant whole-breast radiotherapy for early breast cancer established a 15- or 16-fraction (fr) regimen as standard. The FAST Trial (CRUKE/04/015) evaluated normal tissue effects (NTE) and disease outcomes after 5-fr regimens. Ten-year results are presented. METHODS Women ≥ 50 years of age with low-risk invasive breast carcinoma (pT1-2 pN0) were randomly assigned to 50 Gy/25 fr (5 weeks) or 30 or 28.5 Gy in 5 once-weekly fr of 6.0 or 5.7 Gy. The primary end point was change in photographic breast appearance at 2 and 5 years; secondary end points were physician assessments of NTE and local tumor control. Odds ratios (ORs) from longitudinal analyses compared regimens. RESULTS A total of 915 women were recruited from 18 UK centers (2004-2007). Five-year photographs were available for 615/862 (71%) eligible patients. ORs for change in photographic breast appearance were 1.64 (95% CI, 1.08 to 2.49; P = .019) for 30 Gy and 1.10 (95% CI, 0.70 to 1.71; P = .686) for 28.5 Gy versus 50 Gy. α/β estimate for photographic end point was 2.7 Gy (95% CI, 1.5 to 3.9 Gy), giving a 5-fr schedule of 28 Gy (95% CI, 26 to 30 Gy) estimated to be isoeffective with 50 Gy/25 fr. ORs for any moderate/marked physician-assessed breast NTE (shrinkage, induration, telangiectasia, edema) were 2.12 (95% CI, 1.55 to 2.89; P < .001) for 30 Gy and 1.22 (95% CI, 0.87 to 1.72; P = .248) for 28.5 Gy versus 50 Gy. With 9.9 years median follow-up, 11 ipsilateral breast cancer events (50 Gy: 3; 30 Gy: 4; 28.5 Gy: 4) and 96 deaths (50 Gy: 30; 30 Gy: 33; 28.5 Gy: 33) have occurred. CONCLUSION At 10 years, there was no significant difference in NTE rates after 28.5 Gy/5 fr compared with 50 Gy/25 fr, but NTE were higher after 30 Gy/5 fr. Results confirm the published 3-year findings that a once-weekly 5-fr schedule of whole-breast radiotherapy can be identified that appears to be radiobiologically comparable for NTE to a conventionally fractionated regimen.

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Author and article information

Contributors

Yawo A.C. Fiagan

Journal

Journal ID (nlm-ta): Phys Imaging Radiat Oncol

Journal ID (iso-abbrev): Phys Imaging Radiat Oncol

Title: Physics and Imaging in Radiation Oncology

Publisher: Elsevier

ISSN (Electronic): 2405-6316

Publication date PMC-release: 13 May 2022

Publication date Collection: April 2022

Publication date (Electronic): 13 May 2022

Volume: 22

Pages: 85-90

Affiliations

[a ]Iridium Netwerk, Radiation Oncology, Antwerp, Belgium

[b ]Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium

[c ]Faculty of Medicine and Health Sciences, Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), Universiteit Antwerpen, Antwerp, Belgium

[d ]Department of Radiation Oncology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium

Author notes

[* ]Corresponding author at: GZA Hospitals, Sint-Augustinus-Iridium Netwerk, Oosterveldlaan 24, 2610 Wilrijk, Antwerp, Belgium. Yawo.Fiagan@ 123456gza.be

Article

Publisher Item ID: S2405-6316(22)00043-4

DOI: 10.1016/j.phro.2022.05.003

PMC ID: 9117915

PubMed ID: 35602547

SO-VID: d4b11bb5-9133-4a7c-a835-9558219f0fb5

License:

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

History

Date received : 24 December 2021

Date revision received : 4 May 2022

Date accepted : 5 May 2022

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Comparing treatment uncertainty for ultra- vs. standard-hypofractionated breast radiation therapy based on in-vivo dosimetry

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Abstract

Background and purpose

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Most cited references 34

Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial

Innovations in image-guided radiotherapy.

Ten-Year Results of FAST: A Randomized Controlled Trial of 5-Fraction Whole-Breast Radiotherapy for Early Breast Cancer

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