Hypofractionated Radiotherapy in Breast Cancer

Study Overview
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Brief Summary
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As the number of breast cancer (BrCA) survivors has markedly increased, clinicians are now seeking to reduce treatment-related toxicities and inconveniences of treatment, namely the traditional 6 weeks of daily radiation treatment (XRT). Skin thickening, fibrosis, and edema are some of the most common acute and potentially long-term debilitating toxicities of BrCA XRT. The purpose of this study is to learn if three weeks of daily radiation treatment (RT) to the breast is safe in breast cancer patients who are usually prescribed 6 weeks of daily radiation after breast surgery (e.g. lumpectomy or mastectomy) as standard of care.

Detailed Description
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As the number of breast cancer (BrCA) survivors has markedly increased, clinicians are now seeking to reduce treatment-related toxicities and inconveniences of treatment, namely the traditional 6 weeks of daily radiation treatment (XRT). Skin thickening, fibrosis, and edema are some of the most common acute and potentially long-term debilitating toxicities of BrCA XRT. The purpose of this study is to learn if three weeks of daily radiation treatment (RT) to the breast is safe in breast cancer patients who are usually prescribed 6 weeks of daily radiation after breast surgery (e.g. lumpectomy or mastectomy) as standard of care. Investigators seek to assess the rate of cutaneous toxicity, the rates of lymphedema determined by arm measurements and Grade 3 brachial plexopathy in patients receiving regional nodal irradiation, as well as local control, quality of life, and fatigue levels.

Official Title
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A Pilot Study of Hypofractionated Simultaneous Integrated Boost Radiotherapy in Stage 0, I and III Breast Cancer Patients

Conditions
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Inflammation, Cancer, Breast

Intervention / Treatment
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* Radiation: Hypofractionated Simultaneous Integrated Boost Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have one or more of the following characteristics and be eligible for breast or chest wall with or without regional nodal radiotherapy: Prior Chemotherapy for Breast Cancer Greater than 25 cm of breast separation (the largest distance on an axial slice of the planning CT simulation scan between the entry and exit points of the radiation beam on the body) Non-Caucasian Race Less than or equal to 50 years of age Requiring regional nodal irradiation without evidence of N3 disease Exclusion Criteria: Males will be excluded Women who are pregnant or nursing a child may not take part in this study

Ages Eligible for Study
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Maximum Age: 50 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants with Stage 0-III breast cancer<br>Women with Stage 0-III breast cancer, treated with breast conserving surgery or mastectomy and clear margins, will receive 15 doses of radiation over three weeks. | Radiation: Hypofractionated Simultaneous Integrated Boost Radiotherapy<br>* Participants will receive radiotherapy treatments to the whole breast or chest wall to a dose of 2.66 Gy per day x 15 fractions simultaneously with a boost treatment. The boost treatment will be given on the same days as the whole breast treatment. The lumpectomy cavity + scar (in lumpectomy patients) or chest wall scar (mastectomy patients) will receive 0.54 Gy per day x 15 fractions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Per Cutaneous Toxicity Grade (0, 1, 2, 3, 4) | Cutaneous toxicity rate will be assessed by the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) v.3 grading scale. THe NCI CTCAE grades go from 0 to 4. Grade 0: none. Grade 1: Mild or localized; topical intervention indicated. Grade 2: Intense or widespread; intermittent; skin changes from scratching (e.g., edema, papulation, excoriations, lichenification, oozing/crusts); limiting instrumental ADLs. Grade 3-4: Severe or life-threatening. The higher the grade, the worse the outcome. | Duration of Study (Up to 18 months) | 
| Number of Participants With 20% or Greater Increase in Arm Lymphedema Compared to Baseline | Number of Participants with 20% or greater increase in arm lymphedema (compared to baseline arm measurements) will be assessed among breast cancer patients receiving regional nodal irradiation. | Duration of Study (Up to 18 months) | 
| Number of Participants With Grade 3 Brachial Plexopathy | Number of Participants with Grade 3 Brachial Plexopathy will be assessed among breast cancer patients receiving regional nodal irradiation by RTOG and LENT/SOMA scales Brachial plexopathy range minimum 0 and maximum 4. The higher the score, the worse the outcome | Duration of Study (Up to 18 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cutaneous Toxicity Rate Assessed by Ultrasound Tissue Characterizations (UTC) | Ultrasound tissue characterization (UTC) is driven by knowledge of the physics of ultrasound and its interactions with biological tissue, and has traditionally used signal modelling and analysis to characterize and differentiate between healthy and diseased tissue. Change in mean UTC at last assessment (up to 18 months post XRT) was compared to baseline (pre-XRT) measures. | Baseline, end of Follow Up (Up to 18 months) (up to 18 months) | 
| Change in Tumor Necrosis Factor (TNF) - Alpha Levels | Blood will be analyzed for TNF-alpha (TNF)-alpha levels and correlated to the development of cutaneous toxicity. | Baseline, Post Intervention (Up to 18 Months) | 
| Change in Soluble TNF Receptor 2 (sTNFR2) Levels | Blood will be analyzed for soluble TNF receptor 2 (sTNFR2) levels and correlated to the development of cutaneous toxicity. | Baseline, Post Intervention (Up to 18 Months) | 
| Change in Interleukin (IL)-6 Levels | Blood will be analyzed for interleukin (IL)-6 levels and correlated to the development of cutaneous toxicity. | Baseline, Post Intervention (Up to 18 Months) | 
| Change in Interleukin 1 Receptor Agonist (IL-1ra) Levels | Blood will be analyzed for IL-1ra levels and correlated to the development of cutaneous toxicity. | Baseline, Post Intervention (Up to 18 Months) | 
| Change in C - Reactive Protein (CRP) Levels | Blood will be analyzed for CRP levels and correlated to the development of cutaneous toxicity. | Baseline, Post Intervention (Up to 18 Months) | 
| Change in Multidimensional Fatigue Inventory (MFI) Score | The Multidimensional Fatigue Inventory (MFI) is a 20-item self-report instrument designed to measure fatigue. Scores range from 20 to 100.The higher the score, the more fatigued. The higher the maximum change, the greater increase in fatigue a patient feels. | Baseline, end of Follow Up (Up to 18 months) | 
| Change in Pittsburgh Sleep Quality Index (PSQI) Score | The PSQI is a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Scores range from 0 to 21. A score of less than or equal to 5 is associated with good sleep quality. A score greater than 5 is associated with poor sleep quality. The higher the maximum change, the greater increase in sleep disturbances a patient has. | Baseline, End of Follow Up (Up to 18 months) | 
| Change in Perceived Stress Scale (PSS) Score | The PSS is a self-reported instrument used to measure the perception of stress. Scores range from 0 to 40. Score of 20 or higher are considered high stress. The higher the maximum change, the greater increase in stress the patient feels. | Baseline, End of Follow Up (Up to 18 months) | 
| Change in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form Score | The PROMIS Fatigue questionnaire is a self-report tool used to evaluate frequency, duration, and intensity of fatigue over the past seven days. Scores range from 7 to 35. The higher the score, the more fatigue. | Baseline, End of Follow Up (Up to 18 months) | 
| Change in an Inventory of Depressive Symptomatology-Self Reported (IDS-SR) Score | The IDS-SR is a self-reported measure in which participants rate the frequency of depression symptoms within the past seven days. Scores range from 0 to 84, with higher score reflecting greater severity of depressive symptoms. | Baseline, End of Follow Up (Up to 18 months) | 
| Change in Short Form-36 (SF-36) Health Survey Score | The SF-36 is a self-reported survey of health status. Scores range from 0 to 100. Lower scores indicate disability. The higher the score, the less disability. | Baseline, End of Follow Up (Up to 18 months) | 
| Change in Godin Leisure-Time Exercise Questionnaire (GLTEQ) Score | The GLTEQ is a self-reported questionnaire used to measure usual leisure-time exercise habits during a typical seven day period. The GLTEQ specifically inquires about frequency of mild, moderate, and strenuous physical activity done during a typical 7-day period with exercise of more than 15 min or more per day during the previous week. Total score for the Godin leisure-time exercise questionnaire is calculated using this formula.Weekly leisure activity score = (9 × Strenuous) + (5 × Moderate) + (3 × Light). The GLTEQ total score can be broken into three categories: less than 14 points = sedentary 14 - 23 points is = moderately active 24 points or more = active The score ranges from 0 to 119. | Baseline, End of Follow Up (Up to 18 months) | 
| Change in Lent Soma Scale Patient Questionnaire Score | The Lent Soma questionnaire is a self-reported measure of pain. Scores range from 0 to 9. The higher the score, the more pain reported.The higher the maximum change, the more increase in breast pain, the patient is perceiving. | Baseline, End of Follow Up (Up to 18 months) | 
| Change in Breast Pain Level | Participants will be asked to rate their breast pain level on a study specific scale from 0 to 10 where 0 represents no pain, and 10 represents the most extreme pain. The higher the maximum change, the more increase in breast pain, the patient is perceiving. | Baseline, End of Follow Up (Up to 18 months) | 
| Change in Breast Appearance Satisfaction Score | Participants will be asked to rate the look of their breast on a study specific scale from 0 to 10 where 0 represents not happy, and 10 represents very happy. The higher the maximum change, the more increase in happiness with breast appearance the patient is reporting. | Baseline, End of Follow Up (Up to 18 months) | 
| Change in Radiated Breast Appearance Score | Participants will be asked to rate how different the look of their radiated breast is compared to their non-radiated breast on a study specific scale from 0 to 10 where 0 represents no difference, and 10 represents completely different. | Baseline, End of Follow Up (Up to 18 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psychiatry, Radiation Therapy