Breast Cancer
Conditions
Brief summary
This protocol seeks to utilize a novel method of tumor bed boost delivery and to better understand breast cancer radiation response through the analysis of pre-and post-radiation breast tumor samples.
Detailed description
The study team proposes in this trial to build on the favorable results of the intraoperative boost trials but using a preoperative delivery approach. The PI has demonstrated the feasibility of the preoperative approach and successfully completed a Phase I dose-finding partial breast trial. The preoperative approach has several advantages: 1) expensive intra-operative equipment is unnecessary, 2) a small intact breast tumor results in significantly less uninvolved breast tissue receiving high radiation doses which likely decreases toxicity; 3) more accurate targeting of the high-risk areas of subclinical disease surrounding the tumor is possible, 4) smaller treatment volumes are amenable to dose escalation which can further accelerate treatment and improve accessibility for subjects, and 5) the pre-operative approach provides a novel opportunity to study breast cancer radiation response. Radiotherapy to the intact tumor is a relatively rare event in breast cancer irradiation, particularly in the setting of early stage breast cancer. Tumor and normal tissue radiation response remain relatively poorly understood. Markers capable of predicting radiation response are rare indeed. Therefore, paired pre- and post-radiation tissue will be examined for FAS gene expression and compared among the breast cancer subtypes. FAS is the name of a gene ( not an acronym) that is known to play a critical role in the induction of programmed cell death and is an established prognostic marker in breast cancer. Previous study team findings that FAS induction appears to be breast cancer subtype-specific has not been previously observed and provides a possible explanation for the differential rates of tumor response observed clinically in distinct breast tumor subtypes. The study team's preclinical work with FAS suggests a potential role as a radiation response biomarker. The study goal is to validate those findings in this large cohort of diverse breast cancer subjects. However, because preoperative delivery of the boost to the intact tumor is unique, this study will include a secondary cosmetic outcome that includes predefined stopping boundaries for early indications of suboptimal cosmetic outcomes with this novel approach
Interventions
RADIATIONSingle fraction of 7 Gy
All subjects will receive a single 7 Gy fraction of radiotherapy to the intact tumor prior to surgery.
Sponsors
Gateway for Cancer Research
Duke University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Women with a biopsy proven diagnosis of ductal carcinoma in situ or invasive carcinoma of the breast. Biopsy tissue (either slides or block) from outside institutions will be reviewed to confirm diagnosis. 2. Breast preservation candidates (no prior breast or nodal radiotherapy, no imaging evidence of multicentric disease preventing resection through a single incision, no pregnant women, and no comorbid conditions precluding surgery) 3. cTis-T3 cancer judged to benefit (by treating radiation oncologist) from a tumor bed boost 4. Women of child-bearing potential must consent to use adequate contraception during the course of the study: (1) surgical sterilization (such as a tubal ligation or hysterectomy), (2) approved hormonal contraceptives (such as birth control pills, patches, implants or injections), (3) barrier methods (such as a condom or diaphragm) used with a spermicide, or (4) an intrauterine device (IUD). Contraceptive measures such as Plan B (TM), sold for emergency use after unprotected sex, are not acceptable methods for routine use. 5. White blood cell (WBC) \> 3000, Hgb \> 10, platelets \>100000 within 30 days of consent 6. Eligible for contrasted magnetic resonance imaging( MRI) on initial evaluation with glomerular filtration rate (GFR) ≥ 60 ml/min. A diagnostic MRI ordered within 60 days of diagnosis will be considered an acceptable alternative and will not be repeated. 7. Outside breast imaging will be reviewed at Duke to confirm that findings are consistent with trial eligibility
Exclusion criteria
1. Breast implant in the breast to be treated (contralateral breast implant is acceptable) 2. Medical conditions that may increase risk for poor cosmetic outcome (i.e. Lupus, rheumatoid arthritis, scleroderma) 3. Subjects unable to receive study treatment planning secondary to body habitus or inability to lie flat on the stomach for at least 1 hour 4. Positive serum pregnancy test 5. Insufficient breast imaging to judge clinical stage 6. Subjects without placement of a biopsy clip at the diagnostic procedure who are unwilling to undergo clip placement. 7. Subjects in whom treatment planning constraints cannot be met
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Cosmesis Evaluations Using the NRG Oncology Cosmesis Scale | baseline to 3 years post radiation therapy | Change from baseline rates of cosmesis at 3 years post-treatment as measured by the NRG Oncology cosmesis scale. The scale is scored from 1 (excellent) to 4 (poor) with a lower number representing better physical appearance. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change Circulating Cell Free DNA to Identify Potential Radiation Response Biomarkers | 5 years | Blood collected pre and post treatment will be used to explore the biologic response to radiotherapy by comparing changes in circulating cell-free DNA expression pre and post-radiotherapy: |
| Quality of Life as Measured by Functional Assessment of Cancer Therapy - Breast (FACT-B) Questionnaire | 3 years | Patient-reported Quality of Life as measured by the Functional Assessment of Cancer Therapy - Breast (FACT-B) at 3 years post-treatment. The FACT-B includes 35 items scored on a Likert-type scale from 0 (not at all) to 4 (very much) with a total scale range of 0-140 and a lower total score indicating a better outcome. Only the total scale score is reported; subscales scores are not reported. |
| Composite Review of Local Control | 5-10 years | Document local control in the treated breast relative to historical controls with annual clinical exam and imaging studies. Local control is defined as the time from start of treatment to date of local recurrence estimated using the Kaplan-Meier method. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Single Arm 7 Gray (Gy) Fraction of Radiotherapy All subjects will receive a single 7 Gy fraction of radiotherapy to the intact tumor prior to surgery.
Single fraction of 7 Gy: All subjects will receive a single 7 Gy fraction of radiotherapy to the intact tumor prior to surgery. | 3 |
| Total | 3 |
Baseline characteristics
| Characteristic | Single Arm 7 Gray (Gy) Fraction of Radiotherapy |
|---|---|
| Age, Continuous | 51.67 years STANDARD_DEVIATION 3.79 |
| Cosmesis evaluation | 1 units on a scale STANDARD_DEVIATION 0 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 3 |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
Change in Cosmesis Evaluations Using the NRG Oncology Cosmesis Scale
Change from baseline rates of cosmesis at 3 years post-treatment as measured by the NRG Oncology cosmesis scale. The scale is scored from 1 (excellent) to 4 (poor) with a lower number representing better physical appearance.
Time frame: baseline to 3 years post radiation therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single Arm 7 Gray (Gy) Fraction of Radiotherapy | Change in Cosmesis Evaluations Using the NRG Oncology Cosmesis Scale | 0 score on a scale |
Secondary
Change Circulating Cell Free DNA to Identify Potential Radiation Response Biomarkers
Blood collected pre and post treatment will be used to explore the biologic response to radiotherapy by comparing changes in circulating cell-free DNA expression pre and post-radiotherapy:
Time frame: 5 years
Population: Data not collected.
Secondary
Composite Review of Local Control
Document local control in the treated breast relative to historical controls with annual clinical exam and imaging studies. Local control is defined as the time from start of treatment to date of local recurrence estimated using the Kaplan-Meier method.
Time frame: 5-10 years
Population: Data will not be collected and reported as the study was terminated prematurely due to poor accrual.
Secondary
Quality of Life as Measured by Functional Assessment of Cancer Therapy - Breast (FACT-B) Questionnaire
Patient-reported Quality of Life as measured by the Functional Assessment of Cancer Therapy - Breast (FACT-B) at 3 years post-treatment. The FACT-B includes 35 items scored on a Likert-type scale from 0 (not at all) to 4 (very much) with a total scale range of 0-140 and a lower total score indicating a better outcome. Only the total scale score is reported; subscales scores are not reported.
Time frame: 3 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single Arm 7 Gray (Gy) Fraction of Radiotherapy | Quality of Life as Measured by Functional Assessment of Cancer Therapy - Breast (FACT-B) Questionnaire | 11.7 score on a scale | Standard Deviation 7.5 |