Clinical trial NCT04282122: Clinical Database of Safe Personalized Adjuvant Breast Radiotherapy Based on Individual Radiosensitivity
Official title: Establishment of a Prospective Evaluation of Daily Practice Including the Individual Radiosensitivity Test to the Decision of Daily Practice
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Breast Cancer
Keywords: breast cancer
oncology
database
radiotherapy
Lead sponsor: Institut du Cancer de Montpellier - Val d'Aurelle
Sponsor class: OTHER
First posted: 2020-02-24
Enrollment: 500
Sex: FEMALE
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients treated with safe adjuvant therapy by personalized radiation based on individual radiosensitivity after resection of breast tumor

Brief summary: Severe but also moderate toxicities after curative-intent radiotherapy (RT), such as a poor cosmetic outcome following breast cancer can have a negative impact on quality of life and a marked effect on subsequent psychological outcome. Nevertheless, current practice standards commonly prescribe radiation dose and volume without regard to individual radiosensitivity.

In that context, a normal tissue radiosensitivity test that includes a rapid (72 h) radiosensitivity assay based on flow cytometric assessment of radiation-induced CD8 T-lymphocyte apoptosis (RILA) and other significant clinical parameters (multifactorial nomogram) was developed.

Omission of radiotherapy has been suggested when luminal A tumor subtype is combined with clinical and pathologic factors defining a subgroup of patients with a low risk of ipsilateral breast recurrence. In this group, the benefits of radiotherapy are small \[6\].

Reduction of the breast irradiated volume is also a possibility that has been tested and published using IORT, brachytherapy or external beam radiotherapy.

Hypofractionation has been adapted to breast cancer radiotherapy. Overall, all recent clinical trials \[13, 14\] showed only few late effects when hypofractionation was delivered to the whole breast (WB). These results reinforce the need of patients' selection using the NovaGray Breast® test.

Our hypothesis is therefore that the different techniques (volume reduction or hypofractionation) as well as radiotherapy omission will significantly reduce grade ≥2 bf+ in a personalized approach (driven by a predictive assay of late effects) compared to WB hypofractionation in a selected population at low risk of breast recurrence.

We would like to establish a prospective evaluation of daily practice including the individual radiosensitivity test to the decision of daily practice

Detailed description: Severe but also moderate toxicities after curative-intent radiotherapy (RT), such as a poor cosmetic outcome following breast cancer can have a negative impact on quality of life and a marked effect on subsequent psychological outcome. Nevertheless, current practice standards commonly prescribe radiation dose and volume without regard to individual radiosensitivity.

In that context, a normal tissue radiosensitivity test that includes a rapid (72 h) radiosensitivity assay based on flow cytometric assessment of radiation-induced CD8 T-lymphocyte apoptosis (RILA) and other significant clinical parameters (multifactorial nomogram) was developed. The NovaGray Breast® test combines both a biological analysis (radio-induced lymphocyte apoptosis) and a predictive analysis, including external parameters related to the patient and her treatment. A negative predictive value (\>90%) was found in case of high RILA taken alone and a sensitivity of 80% to detect the toxicity with an initial AUC of 0.61. In addition, including significant clinical parameters, the AUC was increased to 0.69. Moreover, a prognosis model with RILA alone to predict the probability to develop a toxicity and performance of the model was increased with the inclusion of significant clinical parameters (C-Harell 0.61 \>\> 0.69).

The NovaGray Breast® test is now validated after two prospective trials, one French (PHRC) and one European (Requite FP7). RILA and other factors have been confirmed to be independent factors that increase significantly the appearance of severe breast fibrosis. All these data have been merged into a nomogram allowing a predictive tool for daily clinical practice and then to customize radiotherapy techniques and indications.

In the meantime, several treatment modifications have been suggested to reduce late effects after breast radiotherapy:

Omission of radiotherapy has been suggested when luminal A tumor subtype is combined with clinical and pathologic factors defining a subgroup of patients with a low risk of ipsilateral breast recurrence. In this group, the benefits of radiotherapy are small \[6\]. In addition, low risk of recurrence was confirmed in randomized trials in a highly selected population. However, omitting radiotherapy and using intrinsic subtyping and clinical factors is a substantial change in care and could be driven by the risk of toxicity.

Reduction of the breast irradiated volume is also a possibility that has been tested and published using IORT, brachytherapy or external beam radiotherapy. The first two techniques are reserved for trained and expert centres but showed encouraging results with low toxicity rates and recurrences. The recent experience of external partial breast irradiation (EPBI) with twice daily fractions regimen showed an increase risk of late side-effects leading to use hypofractionated EPBI (hEPBI) once daily, 5 days a week. This regimen could only be used in case of selecting patients with NovaGray Breast®test without individual risk of late effects.

Hypofractionation has been adapted to breast cancer radiotherapy. Overall, all recent clinical trials showed only few late effects when hypofractionation was delivered to the whole breast (WB). Nevertheless, It has been shown in the TRANS-FAST trial a significant decrease of grade ≥2 bf+ for increasing values of RILA in the same extent than observed with conventional fractional schedules. These results reinforce the need of patients' selection using the NovaGray Breast® test.

Eligibility criteria: Inclusion Criteria:

1. Compliant women ≥ 65 years old.
2. Conservative breast cancer surgery.
3. T1-T2; N sentinel negative/N0.
4. Luminal A tumors.
5. Tumor negative margins.
6. Indication of whole breast irradiation only.
7. Extension evaluation of disease will be proven negative (M0).
8. Must be geographically accessible for follow-up.
9. Written and dated informed consent.
10. Affiliated to the French social security system.

Exclusion Criteria:

1. Patients with distant metastases.
2. Indications of node irradiation.
3. Synchronous bilateral breast cancer.
4. Patients treated by radical mastectomy.
5. Patients with neoadjuvant therapy.
6. Patients with previous or concomitant other (not breast cancer) malignancy within the past 3 years EXCEPT adequately treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix. Patients who have had a previous other malignancy must have been disease free for at least three years.
7. Patients with other unstable or untreated non-malignant systemic diseases (cardiovascular, renal, hepatic, lung embolism, etc.) which would prevent prolonged follow-up.
8. Patients treated with systemic investigational drugs within the past 30 days

Primary outcomes:
measure: Acute and late breast fibrosis rate
timeFrame: Until the study completion: 5 years
Secondary outcomes:
measure: Quality of life according to the EORTC QLQ-C30
timeFrame: Until the study completion: 5 years
Other outcomes:
Locations:
city: Montpellier
country: France
facility: Institut Régional du Cancer de Montpellier
state: Occ
Study officials:
affiliation: Institut Régional du Cancer de Montpellier (ICM)
name: Céline BOURGIER, MD
role: STUDY_CHAIR
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