Breast CancerIpomammellaNCT03077191
Toxicity and Outcome of Whole Breast Hypofractionated Radiotherapy: a Single Institution Experience
An observational study of Breast Cancer and Quality of Life, run by IRCCS San Raffaele at 1 site in Italy.
Trial summary
This is a homogeneous, single institution, observational, non-interventional, prospective study of 500 patients who will be treated according to the standard protocol of adjuvant hypofractionated radiotherapy after breast conserving surgery, at a total dose of 40 Gy/ 15 fr (5 fr/ week, 3 consecutive weeks). Read more about this study
- Who is it for?
- Ages 18 to 85 years, women only
- Conditions the study is for
- Breast Cancer, Quality of Life, Radiotherapy; Adverse Effect, Dermatitis or Eczema
- What is being tested?
- Quality of life measurement
- How many people
- 410 participants
- Where
- 1 siteItaly
- Study dates
- 1 Nov 2016to 31 Dec 2027
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: Breast cancer patients treated with surgery (conservative/mastectomy), and hypofractionated/ultrahypofractionated radiotherapy to surgical bed or whole breast +/-SIB, +/- regional lymph nodes
Who may be able to join
- Breast cancer patients with TNM Classification of Malignant Tumours pathological stage Tis-T4d, N0-N3, treated with surgery (conservative or mastectomy), accelerated partial breast irradiation or whole breast hypofractionated radiotherapy +/-SIB +/- regional lymph node irradiation
Who cannot join
- male breast cancer patients
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Toxicity and Outcome of Whole Breast Hypofractionated Radiotherapy Without Boost: Results of a Homogeneous Single Institution Experience
This is a homogeneous, single institution, observational, non-interventional, prospective study of 500 patients who will be treated according to the standard protocol of adjuvant hypofractionated radiotherapy after breast conserving surgery, at a total dose of 40 Gy/ 15 fr (5 fr/ week, 3 consecutive weeks). In addition to the regular follow up, the patients will respond to the quality-of-life questionnaires (QLQ) of the European Organisation for Research and Treatment of Cancer (EORTC), general, QLQ- C30, and specific for breast (BR), QLQ- BR23, at the first visit, at the end of radiotherapy and at the subsequent follow-up visits from 6 months up to 5 and a half years, to evaluate the quality of life during and after the treatment.
The study also has a retrospective arm of approximately 3300 patients (number of patients and characteristics of disease expanded with the amendment presented to the Lombardia 1 Ethics Committee in May 22/2024), treated from January 2009, for whom disease control and toxicity will be evaluated.
Read the detailed description
The study is observational, homogeneous (performed in a single institution), non-interventional, and composed of two parts: one retrospective and one prospective (for which we request the registration in the register of clinical trials).
The patients with breast cancer treated with adjuvant hypofractionated radiotherapy at the Department of Radiotherapy of "San Raffaele Scientific Institute" (IRCCSSRaffaele) from January 2009 will be identified and their clinical and dosimetric data retrieved and analyzed.
The objectives of the retrospective arm of the study are the analysis, with a follow up of 5 years, of acute and late toxicity, and clinical outcomes, such as local and regional control, overall survival, disease free survival and cancer-specific survival. A secondary objective is the identification of prognostic factors for toxicity and disease progression.
With the amendment approved by the Ethics Committee 1 of Lombardy Region in 22/05/2024 (CET Em. 195-2024) the number of patients in the retrospective arm was expanded to 3300. Were included: patients treated with moderate hypofractionated or ultra-hypofractionated radiotherapy to whole breast+/- simultaneous integrated boost to surgical bed, patients treated with accelerated partial breast irradiation, patients treated with hypofractionated radiotherapy to regional nodal irradiation and whole breast+/-SIB to surgical bed. The follow-up period was expanded to 10 years.
The objective of the prospective arm of the study, for a cohort of 500 consecutive patients who agree to participate in the study, is to assess the quality of life of the patients treated with hypofractionated short course (3 weeks) radiotherapy. The quality-of-life questionnaires (QLQ) of the European organization for research and treatment of cancer (EORTC): QLQ-C30 (general) and QLQ-BR23 (specific for the breast), will be distributed before radiation treatment, at the time of patient enrollment, at the end of therapy and during the follow up visits, for a duration of 5 years after the first follow up, scheduled first at 6 months and then annually.
Given the non-interventional, observational nature of the study, the follow up program of the patients with breast cancer, treated according to the standard departmental protocol, will not be modified. The patients will be identified from the patient data base from medical records retrieved from the radiotherapy archive, and the images monitoring local evolution from the photo archive. The data will be extracted from medical records. In addition, the dosimetric data of the treatments will be recovered from the physical dosimetric archives and the extrapolated data will be correlated with clinical and toxicity outcomes.
For the patients of the prospective observational arm, the dosimetric data and quality of life questionnaires, as well as the follow up visit results, will be prospectively collected, registered in a data base, and subsequently analyzed.
The toxicity registered during the visits carried out during the treatment will be determined using the Radiation Therapy Oncology Group (RTOG) scale; the Scoring system of late effects of radiation on normal tissues (SOMA-LENT scale) will be used for toxicity registered during the follow up visits. The clinical points analyzed will include: quality of life, overall survival, disease free- and cancer specific-survival, local and regional control, distant metastasis free survival, acute and late toxicity, physical dosimetry and aesthetic results. The correlation between detected parameters will be evaluated for the identification of prognostic factors. Statistical analyses will be performed with SPSS software version 17.0 (SPSS Inc. Released 2008; SPSS Statistic for Windows, Version 17.0. Chicago, USA: SPSS Inc.) and MedCalc v.12.1.4.0 (MedCalc Software, Ostend, Belgium) and any updated version. Statistical tests to be used will include: uni- and multi-variate logistic regression to define predictors of incidence and prevalence of toxicity and local/ distant relapses; Cox model ( proportionally-hazard regression) uni- and multi-variate for actuarial analysis of predictors of toxicity and local/ distant relapses; Wilcoxon matched -pair test for the quality of life index variations; Spearman test for the correlation between continuous variables, ANOVA test for the effect of treatment variables on changes in QoL scores over time.
*Enrollment in the quality-of-life study was suspended in November 2021 due to patients' refusal to participate during the Sars-Cov2 pandemic, the adoption of shorter schedule protocols to minimize patient hospital visits, the adoption of a simultaneous integrated boost for patients with high risk of local relapse(TNBC, HER2+) requiring a change in the technique utilized.
- Conditions
- Breast Cancer, Quality of Life, Radiotherapy; Adverse Effect, Dermatitis or Eczema, Survivorship
- Being tested
- Quality of life measurement
- Keywords
- hypofractionated whole breast radiotherapy, breast cancer, conservative treatment, quality of life
- Medical subject headings
- Breast Neoplasms, Dermatitis, Eczema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Quality of life measurementOther
The quality of life of breast cancer patients treated with conservative surgery and adjuvant whole breast hypofractionated radiotherapy, without boost, will be evaluated.
| Study group | Role | What they receive |
|---|---|---|
| Quality of life | Quality of life of breast cancer patients treated with conservative surgery (quadrantectomy) and adjuvant hypofractionated whole breast radiotherapy according to the institutional standard regimen, to a total dose of 40 Gy in 15 fraction over 3 weeks will be measured with EORTC quality of life questionnaires QLQ-C30 and QLQ-BR23, before the start of the radiotherapy, at the end of the radiotherapy and subsequently at every follow-up visit (the first at 6 months after the end of the treatment, then annually for 5 consecutive years after the first follow up visit). Receives: Other: Quality of life measurement | |
| Breast cancer, retrospective | In the observational retrospective cohort patients with histologically confirmed breast cancer treated with hypofractionated/ultrahypofractionated radiotherapy to: * whole breast +/- Simultaneous Integrated Boost (SIB) to surgical bed, * breast/chest wall and lymph node areas +/- SIB to surgical bed, * surgical bed only, with accelerated partial breast irradiation, using 3D conformal radiotherapy or advanced radiotherapy techniques (IGRT, IMRT, SBRT) will be included. |
What is being measured
The primary outcome is the main question the study is designed to answer.
quality of life after hypofractionated adjuvant radiotherapy
degree of general quality of life worsening of patients treated with hypofractionated adjuvant radiotherapy after breast conserving surgery assessed with EORTC quality of life questionnaires QLQ C30
Measured: up to 66 months
breast specific quality of life after hypofractionated adjuvant radiotherapy
degree of specific quality of life worsening of patients treated with hypofractionated adjuvant radiotherapy after breast conserving surgery assessed with EORTC quality of life questionnaire QLQ BR23
Measured: up to 66 months
Secondary outcomes (9)
Local Relapse Free Survival
Local control of the disease (at the treated site)
Measured: From the date of radiotherapy end until the date of local progression or date of death from any cause, whichever came first, assessed up to 120 months
Regional Relapse Free Survival
Regional control (at the regional lymph node chains)
Measured: From the date of radiotherapy end until the date of regional progression or date of death from any cause, whichever came first, assessed up to 120 months
Distant Metastases Free Survival
Distant metastasis developed after the treatment
Measured: From the date of radiotherapy end until the date of distant progression or date of death from any cause, whichever came first, assessed up to 120 months
Disease Free Survival
Absence of disease progression during the follow-up
Measured: From the date of radiotherapy end until the date of first documented clinical progression or date of death from any cause, whichever came first, assessed up to 120 months
Cancer Specific Survival
Cancer survival
Measured: From the date of radiotherapy end until the date of death from disease progression, assessed up to 120 months
Overall survival
Survival from all causes
Measured: From the date of radiotherapy end until the date death from any cause, assessed up to 120 months
Acute toxicity
Acute toxicity after hypofractionated whole breast adjuvant radiotherapy evaluated with CTCAE (Common Terminology Criteria for Adverse Events) scale v 5.0, which displayes grades from 1 to 5, with grade 1 mening mild toxicity and grade 5 death related to toxicity
Measured: Up to three months from the start of radiotherapy
Late toxicity
Toxicity developed after three months until the end of follow-up or death, assessed with Common Terminology Criteria for Adverse Events (CTCAE) v5.0 scale, which displayes grades from 1 to 5, with grade 1 meaning mild toxicity and grade 5 death related to toxicity
Measured: From three months after the start of radiotherapy until the end of follow-up or death, assessed up to 120 months
Late skin toxicity
Toxicity developed after three months until the end of follow-up or death, assessed with LENT-SOMA scale, which displayes grades from 1 to 4, with grade 1 meaning mild toxicity and grade 4 worst toxicity
Measured: From three months after the start of radiotherapy until the end of follow-up or death, assessed up to 120 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2017
- Study start1 Nov 2016
- Primary completion30 Nov 2026 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (37)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 410 participants (actual)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Andrei Fodor, MD, IRCCS San Raffaele
- Investigators
- Andrei Fodor, M.D., Principal investigator, IRCCS San Raffaele Scientific Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03077191
- Sponsor's protocol ID
- Ipomammella
- Acronym
- Ipomammella
- Status last verified
- Oct 2026
- First submitted
- 16 Feb 2017
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The data that support the findings of this study (anonymized individual participant data) are available on request from the corresponding author to researchers who provide a methodologically sound proposal. Requests made to the corresponding author (AF) will be evaluated by the Lombardy Territorial Ethics Committee 1.
Publications
AIRTUM Working Group. Italian cancer figures, report 2009: Cancer trend (1998-2005). Epidemiol Prev. 2009 Jul-Oct;33(4-5 Suppl 1):1-168. English, Italian.
PubMed 20124636Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer. 2010 Mar;46(4):765-81. doi: 10.1016/j.ejca.2009.12.014. Epub 2010 Jan 29.
PubMed 20116997http://www.istat.it/dati/dataset/20100129_00/
Crocetti E; Airtum Working Group. [Numbers. Cancer survival in Italy is within the European average]. Epidemiol Prev. 2008 Jul-Oct;32(4-5):265. No abstract available. Italian.
PubMed 19186510Airtum Working Group. [Numbers (Airtum Working Group). Survival prospects change with time]. Epidemiol Prev. 2008 May-Jun;32(3):136. No abstract available. Italian.
PubMed 18828550Gotzsche PC, Nielsen M. Screening for breast cancer with mammography. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD001877. doi: 10.1002/14651858.CD001877.pub2.
PubMed 17054145Veronesi U, Cascinelli N, Mariani L, Greco M, Saccozzi R, Luini A, Aguilar M, Marubini E. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med. 2002 Oct 17;347(16):1227-32. doi: 10.1056/NEJMoa020989.
PubMed 12393819Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, Jeong JH, Wolmark N. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002 Oct 17;347(16):1233-41. doi: 10.1056/NEJMoa022152.
PubMed 12393820Agarwal S, Pappas L, Neumayer L, Kokeny K, Agarwal J. Effect of breast conservation therapy vs mastectomy on disease-specific survival for early-stage breast cancer. JAMA Surg. 2014 Mar;149(3):267-74. doi: 10.1001/jamasurg.2013.3049.
PubMed 24429935Vinh-Hung V, Verschraegen C. Breast-conserving surgery with or without radiotherapy: pooled-analysis for risks of ipsilateral breast tumor recurrence and mortality. J Natl Cancer Inst. 2004 Jan 21;96(2):115-21. doi: 10.1093/jnci/djh013.
PubMed 14734701Van de Steene J, Soete G, Storme G. Adjuvant radiotherapy for breast cancer significantly improves overall survival: the missing link. Radiother Oncol. 2000 Jun;55(3):263-72. doi: 10.1016/s0167-8140(00)00204-8.
PubMed 10869741Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans V, Godwin J, Gray R, Hicks C, James S, MacKinnon E, McGale P, McHugh T, Peto R, Taylor C, Wang Y; Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005 Dec 17;366(9503):2087-106. doi: 10.1016/S0140-6736(05)67887-7.
PubMed 16360786Early Breast Cancer Trialists' Collaborative Group (EBCTCG); Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, Cutter D, Davies C, Ewertz M, Godwin J, Gray R, Pierce L, Whelan T, Wang Y, Peto R. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet. 2011 Nov 12;378(9804):1707-16. doi: 10.1016/S0140-6736(11)61629-2. Epub 2011 Oct 19.
PubMed 22019144Veronesi U, Orecchia R, Maisonneuve P, Viale G, Rotmensz N, Sangalli C, Luini A, Veronesi P, Galimberti V, Zurrida S, Leonardi MC, Lazzari R, Cattani F, Gentilini O, Intra M, Caldarella P, Ballardini B. Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomised controlled equivalence trial. Lancet Oncol. 2013 Dec;14(13):1269-77. doi: 10.1016/S1470-2045(13)70497-2. Epub 2013 Nov 11.
PubMed 24225155Vaidya JS, Wenz F, Bulsara M, Tobias JS, Joseph DJ, Keshtgar M, Flyger HL, Massarut S, Alvarado M, Saunders C, Eiermann W, Metaxas M, Sperk E, Sutterlin M, Brown D, Esserman L, Roncadin M, Thompson A, Dewar JA, Holtveg HM, Pigorsch S, Falzon M, Harris E, Matthews A, Brew-Graves C, Potyka I, Corica T, Williams NR, Baum M; TARGIT trialists' group. Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomised trial. Lancet. 2014 Feb 15;383(9917):603-13. doi: 10.1016/S0140-6736(13)61950-9. Epub 2013 Nov 11.
PubMed 24224997