Hypofractionated Radiation Therapy vs Standard Treatment in Breast Cancer.

Study Overview
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Brief Summary
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An explanatory study comparing complementary treatment to breast conservative surgery with radiation therapy DCIS, T1-T2 N0 M0 (AJCC v8) 1 week schedule vs 3.1 weeks standard schedule, in order to determine the equivalence of local tumor control, survival, acute and chronic toxicity. Shorter curse of radiation therapy may lead to similar local control of tumor cells and lower rates of toxicity than 3.1 standard treatment.

Detailed Description
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PRIMARY OBJECTIVE: I. Compare the effectiveness of hypofractionated radiotherapy (1 week) with standard treatment (3.1 weeks) in the local control of breast cancer treated with conservative surgery. SECONDARY OBJECTIVES: I. Identify the histological lineage of the tumor. II. Identify the degree of differentiation of tumor cells. III. Identify the presence and type of receptors (estrogen, progesterone, HER-2NEU) through immunohistochemistry. IV. Measure the frequency of progression or recurrence. V. Identify the site of progression or recurrence. VI. Measure the frequency of toxicity in both groups. VII. Classify toxicity according to its severity. VIII. Classify toxicity according to chronological presentation, acute, subacute, or chronic. IX. Measure quality of life in both groups according to the European Organization for Research and Treatment Cancer scale, Breast Cancer-Specific Quality of Life Questionnaire, (EORTC, QLQ-BR23). X. Measure quality of life in both groups according to the Eastern Collaborative Oncology Group (ECOG) performance scale. XI. Measure 5-year survival. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: will receive radiotherapy treatment with high hypofractionation, 26 Gy in 5 fractions to the whole breast. ARM II: will receive radiotherapy treatment with standard hypofractionation, 42.5 Gy in 16 fractions with simultaneous integrated increase of 5.5 Gy to the tumor bed in high-risk patients. After completion of treatments, patients will be followed: 2 weeks after final fraction, 6 weeks after final fraction, every 4 months for the next 5 years

Official Title
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Hypofractionated Radiation Therapy (1 Week) Compared With Standard Treatment (3.1 Weeks), Evaluation of Local Control of Breast Cancer Treated With Conservative Surgery.

Conditions
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Ductal Breast Carcinoma in Situ, Invasive Breast Cancer, Early-stage Breast Cancer, Stage 0 Breast Cancer, Stage I Breast Cancer, Stage IA Breast Cancer, Stage IB Breast Cancer

Intervention / Treatment
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* Radiation: Hypofractionated radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed by histopathological report of ductal carcinoma in situ (DCIS) or invasive breast carcinoma. Treated with breast-conserving surgery and stage pT1-2 pN0 M0. Over 18 years. Patients who sign informed consent for research study. Exclusion Criteria: Positive nodes. Clinical or pathological stage T3-T4. History of previous irradiation. Postoperative positive margin.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARM I<br>Radiotherapy treatment with high hypofractionation, 26 Gy in 5 fractions to the whole breast. | Radiation: Hypofractionated radiotherapy<br>* Ultra hypofractionated 26 Gy in 5 fractions applied once with daily port film.<br>* Other names: Quality of Life Questionnaire: EORTC QLQ-BR23;|
| Active Comparator: ARM II<br>Radiotherapy treatment with standard hypofractionation, 42.5 Gy in 16 fractions with simultaneous integrated increase of 5.5 Gy to the tumor bed in high-risk patients. | Radiation: Hypofractionated radiotherapy<br>* Ultra hypofractionated 26 Gy in 5 fractions applied once with daily port film.<br>* Other names: Quality of Life Questionnaire: EORTC QLQ-BR23;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identify the progression timing. | Quantify the time to progression through follow up in both groups | 5 years | 
| Identify the recurrence timing. | Quantify the time to recurrence through follow up in both groups | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identify the histological lineage of the tumor | Carcinoma InSitu or Invasive Carcinoma; - Adenocarcinoma - Other | 14 Months | 
| Identify the degree of differentiation of tumor cells | Histologic grade identification using Scarff-Bloom-Richardson (SBR) scale Grade 1: 3-5 points Grade 2: 6-7 points Grade 3: 8-9 points | 14 months | 
| Identify the presence and type of receptors (estrogen, progesterone, HER-2NEU) through immunohistochemistry | Number of participants with presence of Luminal A, B, HER-2NEU enriched or triple negative immunohistochemistry subtype. Luminal A: RE (+), RP >20%, Ki67 <20% y HER 2 NEU (-) Luminal B: RE (+), RP <20%, Ki67 >20% y HER 2 NEU (+/-) HER-2 Enriched: RE (-), RP (-),Ki67 any, HER 2 NEU (+) Triple Negative: RE (-), RP (-), Ki67 any, HER-2 (-) | 14 months | 
| Measure the frequency of toxicity in both groups. | Quantify the presence of toxicity categorized by CTCAE version 5 system. Grade 1: characterized by the presence of a mild adverse event that does not require treatment Grade 2: considers a moderate adverse event that may require medical treatment on an outpatient basis Grade 3: is a serious adverse event that should receive medical treatment, and even hospital treatment. Grade 4: is an adverse event with risk of death or disability that requires specialized medical management and hospitalization. Grade 5: considers the presence of death associated with an adverse event. | 5 years | 
| Classify toxicity according to its severity. | Quantify toxicity according to its severity categorized by CTCAE version 5 system. Dry skin: A disorder characterized by flaky and dull skin; the pores are generally fine, the texture is a papery thin texture - Grade 1 to 3 Eczema: A disorder characterized by skin which becomes itchy, red, inflamed, crusty, thick, scaly, and/or forms blisters. - Grade 1 to 3 Skin hyperpigmentation: A disorder characterized by darkening of the skin due to excessive melanin deposition. - Grade 1 to 2 Dysphagia: A disorder characterized by difficulty in swallowing. - Grade 1 to 4 Cough: A disorder characterized by sudden, often repetitive, spasmodic contraction of the thoracic cavity, resulting in violent release of air from the lungs and usually accompanied by a distinctive sound. - Grade 1 to 3 Pneumonitis: A disorder characterized by inflammation focally or diffusely affecting the lung parenchyma. Grade 1 to 5 | 5 years |