Clinical Trials /

Radiotherapy Omission in Low Risk Ductal in Situ Carcinoma Breast

NCT03878342

Description:

Following breast-conserving surgery (BCS) for localized ductal carcinoma in situ (DCIS) of the breast, whole-breast irradiation (WBRT) is a standard of care, reducing the absolute rate of in-breast recurrences (IBR) by more than 15% at 10 years, from 28% without radiotherapy to 13 % with radiotherapy. Half of the recurrences occurred as invasive disease. Whereas in the comparative trials, WBRT did not impact on overall survival, survival of patients who recurred with invasive cancers was impaired in comparison to patients who did not recur, or to patients with DCIS-only recurrences. Using criteria based on age, tumor size, nuclear grade, and margins status, several trials and cohort studies failed to identify subgroups of patients at low risk, who could be safely spared the need for WBRT. The RTOG DCIS trial included patients treated with BCS for low- or intermediate grade DCIS revealed by unifocal microcalcifications, size ≤25 mm, margins ≥3 mm, and no residual microcalcifications after surgery. The 5-year rates of IBR were 3.5 % without radiotherapy, versus 0.4 % with radiotherapy, and 6.7 % and 0.9 % at 7 years, respectively (p <0.001). Sixty percent of the patients received tamoxifen in both groups. Several studies showed that the same molecular classes were identified in DCIS as in invasive cancers. Studies suggested that low proliferation, hormone receptors expression, and lack of ERBB2 amplification were associated with a low risk of IBR in patients not receiving radiotherapy. A combined signature was tested in the ECOG trial, showing a 10 % IBR rate at ten years in patients with a low-risk. Identifying very low-risk DCIS, using biological markers in addition to the clinical and histological markers of low-risk DCIS, could help to select patients who could be safely avoided WBRT following BCS. It would avoid over-treatment in these women and could decrease the cost of management.

Related Conditions:
  • Breast Lobular Carcinoma In Situ
  • Ductal Carcinoma In Situ
Recruiting Status:

Recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Radiotherapy Omission in Low Risk Ductal in Situ Carcinoma Breast
  • Official Title: Prospective Study of Omission of Whole-breast Radiotherapy Following Breast-conserving Surgery in Patients With Very Low Risk Ductal Carcinoma in Situ of the Breast

Clinical Trial IDs

  • ORG STUDY ID: UC-0107/1803
  • NCT ID: NCT03878342

Conditions

  • DCIS
  • Breast Cancer
  • Low Risk DCIS
  • Breast Conserving Surgery
  • Radiotherapy Omission

Purpose

Following breast-conserving surgery (BCS) for localized ductal carcinoma in situ (DCIS) of the breast, whole-breast irradiation (WBRT) is a standard of care, reducing the absolute rate of in-breast recurrences (IBR) by more than 15% at 10 years, from 28% without radiotherapy to 13 % with radiotherapy. Half of the recurrences occurred as invasive disease. Whereas in the comparative trials, WBRT did not impact on overall survival, survival of patients who recurred with invasive cancers was impaired in comparison to patients who did not recur, or to patients with DCIS-only recurrences. Using criteria based on age, tumor size, nuclear grade, and margins status, several trials and cohort studies failed to identify subgroups of patients at low risk, who could be safely spared the need for WBRT. The RTOG DCIS trial included patients treated with BCS for low- or intermediate grade DCIS revealed by unifocal microcalcifications, size ≤25 mm, margins ≥3 mm, and no residual microcalcifications after surgery. The 5-year rates of IBR were 3.5 % without radiotherapy, versus 0.4 % with radiotherapy, and 6.7 % and 0.9 % at 7 years, respectively (p <0.001). Sixty percent of the patients received tamoxifen in both groups. Several studies showed that the same molecular classes were identified in DCIS as in invasive cancers. Studies suggested that low proliferation, hormone receptors expression, and lack of ERBB2 amplification were associated with a low risk of IBR in patients not receiving radiotherapy. A combined signature was tested in the ECOG trial, showing a 10 % IBR rate at ten years in patients with a low-risk. Identifying very low-risk DCIS, using biological markers in addition to the clinical and histological markers of low-risk DCIS, could help to select patients who could be safely avoided WBRT following BCS. It would avoid over-treatment in these women and could decrease the cost of management.

Trial Arms

NameTypeDescriptionInterventions
RadiotherapyActive Comparatortwo fractionation regimens will be allowed for whole-breast irradiation: 50 Gy in 25 fractions over 5 weeks or 40 Gy in 15 fractions over 3 weeks. The delivery of an additional dose to the tumour bed (boost) will be at the referring physician discretion, according to the guidelines
    No RadiotherapyExperimentalNo Irradiation- Active surveillance

      Eligibility Criteria

              Inclusion Criteria:
      
                1. Woman aged >50 years,
      
                2. Postmenopausal Status; Note: Note: woman is considered post-menopausal if she has had
                   amenorrhea for 12 months or more or has undergone surgical oophorectomy.
      
                3. ECOG performance status ≤2
      
                4. Microcalcifications on pre-operative mammography, unifocal, ≤25 mm;
      
                5. Absence of residual microcalcifications on post-operative mammography;
      
                6. Breast-conserving surgical excision;
      
                7. Histologically proven DCIS of the breast without an invasive component; Note:
                   histological finding of DCIS lesions associated with or developed in a benign breast
                   lesion or in case of a classical LCIS associated with the DCIS are accepted.
      
                8. Free margins (≥2 mm), or free margins following re-excision;
      
                9. Low or Intermediate nuclear grade; Note: In case of nuclear grade heterogeneity, the
                   higher -grade score will prevail.
      
               10. Tumour tissue sample availability; Note: Surgical specimen is mandatory unless no
                   residual disease on the surgical specimen. In this instance, the initial diagnosis
                   biopsy is required.
      
               11. Absence of extensive necrosis;
      
               12. Immunohistochemical characteristics of luminal A subtype: ER ≥10 %, PR ≥20 %, HER2
                   negative (0/1+) or 2+ not amplified (confirmed by FISH or CISH), Ki67 <15%.
      
               13. Patient willing and able to comply with the protocol for the duration of the study
                   including undergoing treatment, scheduled visits and examinations and including
                   follow-up;
      
               14. Written informed consent;
      
               15. Affiliation to the French social security.
      
              Exclusion Criteria:
      
                1. Endocrine treatment for breast cancer;
      
                2. Previous diagnosis of DCIS or invasive cancer, (except basal-cell, carcinoma in situ
                   of the cervix or endometrium);
      
                3. Synchronous bilateral DCIS;
      
                4. Known breast-cancer predisposing germ-cell mutation;
      
                5. Palpable tumour opacity or bloody nipple discharge;
      
                6. Histological evidence of multifocality (defined as having more than one distinct focus
                   of DCIS with >5 mm of intervening benign breast tissue in one quadrant of the breast);
      
                7. High nuclear grade, including high nuclear grade in heterogeneous tumours;
      
                8. Associated microinvasive component;
      
                9. Presence of tumour cells in lymph nodes detected using H&E or immunohistochemical
                   examination (if lymph node sentinel biopsy or dissection has been performed);
      
               10. Absolute contra-indication to whole-breast irradiation as determined by the referring
                   physician;
      
               11. Patient unable to comply with study obligations for geographic, social, or physical
                   reasons, or who is unable to understand the purpose and procedures of the study.
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:51 Years
      Eligible Gender:Female
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:5-year cumulative incidence of in-breast cancer recurrences
      Time Frame:5 years
      Safety Issue:
      Description:Incidence of breast recurrence is determined from the date of last surgery to the date of breast recurrence.

      Secondary Outcome Measures

      Measure:Overall survival (OS)
      Time Frame:10 years
      Safety Issue:
      Description:OS is defined as the interval between the date of last surgery and the date of death from any cause;
      Measure:Breast cancer-specific survival (BCSS)
      Time Frame:10 years
      Safety Issue:
      Description:BCSS is defined as the interval between the date of last surgery and the date of death from breast cancer
      Measure:Relapse-free survival (RFS)
      Time Frame:10 years
      Safety Issue:
      Description:RFS is defined as the interval between the date of last surgery and the date of ipsilateral breast recurrence, regional nodes recurrence, distant metastases, of death from breast cancer, whichever occurs first
      Measure:Rate of in-breast recurrences (IBR).
      Time Frame:10 years
      Safety Issue:
      Description:In-breast recurrence defined as any carcinoma (invasive or in situ) occurring in the treated breast
      Measure:Rate of Contralateral breast
      Time Frame:10 years
      Safety Issue:
      Description:Contralateral breast cancer defined as any carcinoma (invasive or in situ) occurring in the contralateral breast.
      Measure:Quality of life of the patients using EORTC-QLQ-C 30
      Time Frame:3 years
      Safety Issue:
      Description:Quality of life will be assessed using QLQ-C 30 questionnaire from the European Organization for Research and Treatment of Cancer (EORTC). It is a 30-item self-reporting questionnaire developed to assess the quality of life of cancer patients. It is grouped into five functional subscales (role, physical, cognitive, emotional and social functioning). In addition, there are three multi-item symptom scales (fatigue, pain, and nausea and vomiting), individual questions concerning common symptoms in cancer patients,and two questions assessing overall Quality of Life
      Measure:Quality of life of the patients using EORTC-QLQ-BR23
      Time Frame:3 years
      Safety Issue:
      Description:Quality of Life of Patients will be assessed using a EORTC-QLQ BR23.It is a 23-item self-reporting specific questionnaire developed to assess the quality of life of breast cancer patients. It permits to evaluate the symptoms of breast cancer and the side effects of treatment.
      Measure:Cosmetics Evaluation
      Time Frame:3 years
      Safety Issue:
      Description:cosmetic results will be evaluated by centralized photographic analysis.

      Details

      Phase:N/A
      Primary Purpose:Interventional
      Overall Status:Not yet recruiting
      Lead Sponsor:UNICANCER

      Last Updated