Clinical Trial to Evaluate Single Dose Versus Three Doses of Stereotactic Radiation Therapy (SBRT) Prior to Surgery for Early Stage Breast Carcinoma: SIGNAL 2.0 (Stereotactic Image-Guided Neoadjuvant Ablative Radiation Then Lumpectomy) Trial
概览
- 阶段
- 不适用
- 干预措施
- Stereotactic Body Radiation Then Surgery
- 疾病 / 适应症
- Early Stage Breast Carcinoma
- 发起方
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- 入组人数
- 139
- 试验地点
- 1
- 主要终点
- Proliferation markers will be measured
- 状态
- 已完成
- 最后更新
- 2个月前
概览
简要总结
Radiation therapy after surgery to remove breast cancer improves control of the breast cancer. Standard therapy after breast conservation surgery is five to six weeks of radiation to the entire breast.
This clinical trial will evaluate the effectiveness of conformal radiation therapy delivered only to the area in the breast where the lumpectomy will be performed.
This study will determine if radiation therapy delivered in this manner will prevent the cancer from coming back and eliminate the need for five to six weeks of radiation. Eligible participants will be randomized to one of two arms; Arm 1 which is comprised of one neoadjuvant radiation treatment, or Arm 2 which is comprised of three neoadjuvant radiation treatments.
The study will also gather information about the safety and effects (good and bad) this radiation has, the immune priming effects of this radiation, and on patient satisfaction with the appearance of the breast.
详细描述
Our proposal represents the convergence of several recent developments in the treatment of patients with low-risk carcinoma of the breast. For the selected subset of patients with low-risk disease, it appears that intra-operative radiotherapy with a single fraction leads to acceptable clinical outcomes in terms of local control, overall survival and toxicity. There have also been a few Phase I dose escalation trials demonstrating safety with single fraction breast radiation. In this study, we propose the delivery of radiotherapy using stereotactic body radiation therapy in two different regimens; a single 21 Gy fraction, or 3 10Gy fractions. Radiation will be delivered using Volumetric-modulated arc therapy (VMAT), planned on coregistered MRI (with a subset having a 3T PET-MRI) and CT imaging, and delivered prone. Our approach will potentially have numerous benefits, including significantly shortened treatment time, convenience and potentially reduced health care costs. It would significantly improve the quality of life of many patients. This study will also provide a unique opportunity for pathologic assessment of the impact of radiation at a microscopic level and on tumour and immune markers without the confounding impact of systemic treatments, comparing pre- to post-radiation biopsy specimens for imaging and histologic predictors of radiation sensitivity.
研究者
Muriel Brackstone
Principal Investigator
London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
入排标准
入选标准
- •Age ≥ 50 years and postmenopausal
- •Tumor size \< 3cm on pre-treatment imaging
- •Any grade of disease, estrogen receptor (ER) positive
- •Unicentric/unifocal disease
- •Invasive ductal carcinoma or other favorable subtypes of epithelial breast malignancy (lobular, medullary, papillary, colloid, mucinous, or tubular) .
- •Clinically node-negative (based upon pre-treatment physical examination and/or axillary ultrasound).
- •Surgical expectation that a \> 2mm margin can be obtained.
- •Lesion is 1 cm or greater from the skin surface.
- •Able to have surgery within 14-20 days of radiation therapy.
- •Able to lie comfortably in the prone position with arms raised above the head for extended periods of time.
排除标准
- •Previous RT to the same breast
- •Evidence of suspicious diffuse microcalcifications in the breast prior to the start of radiation.
- •Local metastatic spread into ipsilateral axilla and/or supraclavicular region and/or neck nodes and/or internal mammary nodes diagnosed on clinical examination or any imaging assessment (unless such sites can be confirmed as negative following biopsy)
- •Distant metastases
- •Involvement of contralateral axillary, supraclavicular, infraclavicular or internal mammary nodes (unless there is histologic confirmation that these nodes are negative)
- •Prior non-hormonal therapy or radiation therapy for the current breast cancer
- •Patients with Paget's disease of the nipple.
- •Skin involvement, regardless of tumor size.
- •Patients with a breast technically unsatisfactory for radiation therapy.
- •Inability to lie prone with arms raised above head for extended periods of time.
研究组 & 干预措施
Single Fraction
Stereotactic neoadjuvant ablative radiation give in one single dose of 21 Gy. Lumpectomy to follow within 14-20 from radiation treatment date.
干预措施: Stereotactic Body Radiation Then Surgery
Three Fractions
Stereotactic neoadjuvant ablative radiation give in three doses of 10 Gy (30 Gy given in 3 fractions, one treatment every second business day). Lumpectomy to follow within 14-20 days from last radiation treatment.
干预措施: Stereotactic Body Radiation Then Surgery
结局指标
主要结局
Proliferation markers will be measured
时间窗: 1.5 years
Proliferation will be examined using the Ki67 marker, hypoxia will be examined using the Carbonic Anhydrase 9 (CAH IX), or HIF1/HIF2 markers, apoptosis will be examined using the Caspase-3, or Tunnel markers, invasion will be analyzed using the vimentin, or SDF1-a markers.
Hypoxia markers will be measured
时间窗: 1.5 years
Hypoxia will be examined using the Carbonic Anhydrase 9 (CAH IX), or HIF1/HIF2 markers, apoptosis will be examined using the Caspase-3, or Tunnel markers, invasion will be analyzed using the vimentin, or SDF1-a markers.
Invasion markers will be measured
时间窗: 1.5 years
Invasion will be analyzed using the vimentin, or SDF1-a markers.
Toxicity resulting from radiation treatment
时间窗: 1.5 years
Toxicity resulting from radiation treatment will be collected and graded according to the Common Terminology Criteria for Adverse Events, version 4.0
Immune priming will be measured
时间窗: 1.5 years
Immune priming effects of both treatment arms will be evaluated by quantifying tumour infiltrating lymphocytes (CD8) into tumour specimen, as well as the expression of immune markers (PDL1, Fox3) and immune panel in blood (CD4, CD8, neutrophil, and macrophage counts).
Apoptosis markers will be measured
时间窗: 1.5 years
Apoptosis will be examined using the Caspase-3, or Tunnel markers, invasion will be analyzed using the vimentin, or SDF1-a markers.
Angiogenesis will be measured
时间窗: 1.5 years
Angiogenesis will be examined using the CD31 or VEGF-a cell markers
次要结局
- Disease-Free Survival(8.5 years)
- Overall Survival(8.5 years)
- Mastectomy-Free Survival(8.5 years)
- Cosmesis of the treated breast(1.5 years)