Clinical Trials of Proton Therapy for Breast Cancer. Andrew L. Chang, MD 張維安 Study Chair

Clinical Trials of Proton Therapy for Breast Cancer Andrew L. Chang, MD 張維安 Study Chair AndrewLChangMD@gmail.com

Disclosure Proton Center Development Corporation Scripps San Diego Proton Therapy Center ProCure Oklahoma City Proton Therapy Center Hampton University Proton Therapy Institute ProCure Proton Therapy Center, Inc. Varian Medical Systems Sumitomo Heavy Industries SAH Global SAH Global Dubai Proton Therapy Center VOA Advanced Particle Therapy Malaysian Proton Therapy Center

Outline Background Study criteria Study Description Immobilization Techniques Locally advanced breast Cancer

Introduction First written account of cancer circa 3000 BC in the Edwin Smith Papyrus described breast cancer Hajdu SI. Cancer. 2011 Mar 1;117(5):1097-102. doi: 10.1002/cncr.25553. Epub 2010 Oct 19.

PCG BRE007-12 Phase II Protocol of Proton Therapy for Partial Breast Irradiation in Early Stage Breast Cancer

PBI Trial: Impetus Limited data on feasibility, efficacy, safety of PBI Very limited data on feasibility, efficacy, safety of PBI with protons Additional questions regarding immobilization methods, imaging, breast size and PBI Conflicting skin toxicity outcomes of Loma Linda and Mass General trials No data available on proton PBI for patients classified as cautionary or unsuitable for off-protocol treatment by ASTRO consensus statement on PBI

Objectives and Schema Opened to accrual 2013 January Primary Objective: To determine freedom from ipsilateral breast recurrence occurrences in patients receiving partial breast proton radiation therapy at 3 years. Secondary Objective: To assess the acute and long-term toxicity of partial breast irradiation using proton therapy for the treatment of early stage breast cancer. To assess relationship between breast size and partial breast dosimetry. Compare results of post-operative vs. pre-operative partial breast irradiation. Determine quality of life results. To determine overall survival rate of patients with breast cancer treated with proton radiation at 3 years. Lumpectomy Study Registration Within 8 wks after completion of chemotherapy OR Within 12 weeks after surgery Radiotherapy 4.0 Gy (RBE) x10 fractions to 40 Gy (RBE) Total Dose 4 weeks Follow Up per section 4.0

Inclusion/Exclusion Criteria Summary Inclusion Criteria (ASTRO) Female sex Age 50 years old (>60) Tumor size 3cm ( 2cm) AdenoCa or DCIS (no DCIS) Negative surgical margins by at least 2mm ER positive status No EIC, LVSI, or invasive lobular disease SN biopsy or ALND Nodal stage pn0 PCG BRE-007-12 Exclusion Criteria Previous ipsilateral breast cancer Previous RT to ipsilateral breast/thorax Pregnancy Collagen vascular disease ER negative LVSI + Nodal disease BRCA1 or BRCA2 Paget s disease of the nipple Invasive lobular histology Skin involvement Unremoved breast implant

Must sign study-specific, IRB-approved informed consent. Must be female. Must be 50 years of age. Must have a life expectancy of at least 5 years based on age and co-morbidities. Must have pathology proven invasive ductal carcinoma (lobular is not allowed) and/or ductal carcinoma in situ (DCIS). Must have one of the following: Inclusion Criteria Tumors that a microscopically multifocal must be 3.0 cm and encompassed within a single scar Do not have a microscopically multifocal tumor. In the presence of extensive intraductal component (EIC), the entire pathological tumor size (including both intraductal and invasive components) must be 3.0 cm. Must be Stage 0, I, II (T1-2, N0, N0 per AJCC criteria 7 th ed.) If Stage II, the tumor size must be 3.0 cm. A patient with invasive histology must have nodal stage pn0 by H&E stains on sentinel node biopsy or axillary lymph node dissection.

Inclusion Criteria Must have ER positive disease with ER/PR report available. Must have HER2 performed/report available (positive or negative allowed). Must have Oncotype performed on core and lumpectomy and results available. Must have lumpectomy performed, with documented negative surgical margins > 0.2 cm. If re-excision results in negative surgical margins > 0.2 cm, patient is eligible. Must be prepared to have 3 fiducial markers minimum; 4 preferred, placed prior to treatment if not previously done: If markers or clips were placed at the time of surgery, must be able to start treatment within 12 weeks after lumpectomy or re-excision for clean margins. If markers were not placed at the time of surgery, must have markers placed within 6 weeks after surgery. If systemic chemotherapy was given, patients must have had clips or markers placed at the time of surgery, and must have simulation scans within 6 weeks of the completion of chemotherapy. Must be able to start treatment within 12 weeks of surgery OR 8 weeks of finalization of chemotherapy.

Previous history of ipsilateral invasive breast cancer or DCIS. Any clinically or radiographically suspicious nodes, unless biopsy proven benign. Non-epithelial malignancies such as sarcoma or lymphoma. Suspicious microcalcifications of either breast, unless negative for malignancy on pathology. Multicentric or bilateral disease unless biopsy of the clinical abnormalities are performed and result is negative. Lymphovascular space invasion (LVSI) on pathology specimen. Any previously treated breast carcinoma or synchronous breast carcinoma in ipsilateral breast. Prior radiation therapy to the ipsilateral breast or thorax. Paget s disease of the nipple. Histological examination showing invasive lobular histology. Skin involvement. Exclusion Criteria

Breasts technically unsatisfactory for radiation treatment upon the discretion of the treating physician Ipsilateral breast implant unless removed prior to radiation treatment. Significant infection or other co-existing medical condition that would preclude protocol therapy such as pregnancy, HIV/AIDS or collagen vascular diseases specifically systemic lupus erythematosis, scleroderma, or dermatomysositis. Known BRCA 1 or BRCA 2 mutation. Pregnant or lactating. Exclusion Criteria

Treatment Details Timing RT start within 12 weeks of lumpectomy (or last re-excision lumpectomy OR RT start within 8 weeks of last chemotherapy cycle RT Details: (with fiducials in tumor bed) Volumes: GTV consists of tumor bed visualized by CT or MRI (MR simulation optional) CTV = GTV + 1.5 cm expansion and anatomically constrained by skin & muscle PTV = GTV + 0.5 cm geometrically Dose: 40 Gy(RBE) in 10 fractions with 4 Gy(RBE) per fraction One fraction per day Two fields minimum per day

Patient Assessments Baseline Photographs QOL (BCTOS scale) Cosmesis Weekly During RT Adverse Event assessment At 4 weeks following RT: Adverse Event assessment Follow Up (annually Yrs 1-5, then every 2 years) Year 1, 3 History and Physical Exam Adverse Event assessment Bilateral mammogram QOL questionnaire MD reported Cosmesis Breast photographs Year 2, 4, 5 Bilateral mammogram History and Physical Exam Adverse Event assessment Year 7+ Bilateral Mammogram annually (even after Year 5) History and Physical Exam Adverse Event assessment

Failure Pattern Diagnosis of Breast Cancer Recurrence: Ipsilateral Breast Tumor Recurrence (IBRT) Histologically proven invasive or in situ breast cancer (non-lobular carcinoma in situ (LCIS)) in the tumor bed or within 3cm of any of the markers Ipsilateral Second Primary Histologically proven invasive or in-situ breast cancer (non-lcis) at least 3 cm from all markers Regional Recurrence Tumor in the ipsilateral axillary, infraclavicular, ipsilateral supraclavicular or internal mammary lymph nodes. This can be either biopsy proven or highly suspicious clinically on imaging such as PET scan Distant Recurrence Skin, subcutaneous tissue, and lymph nodes (other than local or regional metastatic).

IMMOBILIZATION Partial decubitus supine immobilization

Partial Decubitus Supine

PCG BRE008: Phase II Study of Postoperative, Cardiac- Sparing Proton Radiotherapy for Patients with Stage II/III Loco-Regional, Non-Metastatic Breast Cancer Requiring Whole Breast or Chest Wall Irradiation with Lymph Node Irradiation Major Inclusion Criteria Female sex Age 18 years old Invasive ductal or lobular CA Stage II-III Negative surgical margins ER positive status No prior history of breast CA No prior RT of the breast / thorax Surgery Study Registration Radiotherapy Chest Wall / Whole breast (+AxLN & SCV): 45 50.4 Gy (1.8 Gy / fx) + Boost to 61.2 66.6 Gy 4 weeks Follow Up per section 4.0

Thank you! Questions? Andrew L. Chang, MD 張維安 AndrewLChangMD@gmail.com

Q-FIX K-VUE TABLE ACCESS 360 PRONE BEAST TABLE

Q-fix K-Vue Access 360

CT Table Q-fix K-Vue Access 360