1. Particle Therapy Cooperative Group North America Annual Conference
Chicago, October 23-25, 2017

2. Excellent Acute Toxicity Outcomes with Proton Therapy for Partial Breast Irradiation in Early Stage Breast Cancer: Initial Results of a Multi-institutional Phase II Trial
J. Isabelle Choi, MD California Proton Therapy Center San Diego, California

3. Disclosures Andrew L. Chang: Proton Center Development Corporation
Hampton University Proton Therapy Institute
ProCure Oklahoma City Proton Therapy Center
ProCure Proton Therapy Center, Inc.
Varian Medical Systems
Sumitomo Heavy Industries
SAH Global Bahrain Proton Therapy Center
SAH Global Oman Proton Therapy Center
SAH Global Dubai Proton Therapy Center
VOA
Advanced Proton Therapy
Scripps San Diego Proton Therapy Center
Malaysian Proton Therapy Center

4. Background
Partial breast irradiation (PBI) with proton beam therapy (PBT) after lumpectomy for early stage breast cancer is an area of active investigation

5. Dosimetric Advantage of Proton Beam Therapy for PBI
PBT allows for superior sparing of normal breast tissue and other surrounding organs of interest (heart, lung)

6. Institutional Experiences
MGH (Gallan-Girodet S, et al., IJROBP 2014; Kozak KR, et al., IJROBP 2006)
Phase I, 19 pts treated with PBT (1-3 fields) and 79 pts treated with photons or mixed photons/electrons, 32 Gy in 8 fractions BID.
At 7 years f/u, 62% physician-reported good-excellent cosmesis, increased acute and late skin toxicity versus photon therapy. Excellent disease control (6% local failure).
National Cancer Center, Korea (Chang JH, et al., Radiother Oncol 2013)
Phase II, 30 patients treated with PBT (1-2 fields), 30 Gy in 5 fractions QD.
Median f/u 5 years. 69% physician-reported good-excellent cosmesis at 3 years - increased toxicity with single field plan. No local or distant failures.
Loma Linda University (Bush DA, et al., IJROBP 2014; Bush DA, et al., Clin Breast Ca 2011)
Phase II, 50 patients treated with PBT (2-4 fields), IDC ≤3 cm s/p lumpectomy, 40 Gy in 10 fractions QD.
Median f/u 48 months. 4 pts with grade 2 acute skin toxicity; 90% good- excellent cosmesis. No local failures.

7. Primary Aim
To investigate the feasibility, safety, and efficacy of delivering PBI with proton beam therapy in a multi- institutional setting

8. Proton Collaborative Group (PCG) BRE007-12 trial
Participating sites:
Hampton University Proton Therapy Institute (HUPTI)
ProCure PTC Oklahoma City
Northwestern Medicine Chicago Proton Center
Eligibility:
Age >50 years
ER+
pN0
IDC and/or DCIS ≤3 cm s/p lumpectomy with >2 mm margins
Excluded:
Prior RT, LCIS, ILC, multicentric disease

9. Radiation Therapy
Proton beam therapy (all uniform scanning except one patient treated with passive scatter)
40 Gy / 4 Gy x 10 daily fractions
Minimum 3 fields used; minimum 2 fields treated daily
CTV = GTV cm radial margin
3 mm retraction at skin and pec m.

10. Statistics and Accrual
Primary endpoint
Freedom from ipsilateral breast recurrence
Primary analysis
Null hypothesis: FFF of ipsilateral breast cancer recurrence is 85% or lower
Alternate hypothesis: FFF of ipsilateral breast cancer recurrence is 97% or higher
Powered to have a 95% probability of rejecting the null hypothesis
Planned sample size: 42
Accrual
N = 42 from Feb 2013 to Nov 2016
40 patients initiated protocol treatment
Current analysis with data through Jun 2017

11. Study Endpoints Secondary endpoints Additional endpoints
Acute toxicity
Evaluated qweek with NCI CTCAE v4.0 toxicity grading scale
Patient-reported QOL
Breast Cancer Treatment Outcome Scale (BCTOS) at baseline prior to RT, and at 1 year and 3 years post-treatment
BTCOS scored 1-4 (1: none; 2: mild; 3: moderate; 4: large)
Physician-reported cosmesis assessment
Including photographs at pre-treatment baseline, and at 1 year and 3 years post-treatment
Correlation of DVH with ipsi breast volume on CT and bra cup size
Additional endpoints
Disease Control (ipsi second primary, regional recurrence, distant recurrence, RFS, OS, contralateral breast cancer, secondary primary cancer)

12. Results
Median follow-up: months
(range 2-36 months)

13. Results: Disease Control
Primary endpoint
Freedom from ipsilateral breast cancer recurrence: 100%
Distant disease control: 100%
One patient developed a new hormone receptor- negative IDC of the contralateral breast

14. Results: Toxicity Acute toxicity (CTCAE v4.0)
Grade 2: 6 events (1 - radiation dermatitis, 1 - lymphedema, 3 - hot flashes, 1 – fatigue)
Grade 3: 1 event (occurred 3 weeks after RT completion in the form of vascular disease requiring stent placement -- highly unlikely to be attributable to RT effects)
Patient-reported QOL (BTCOS)
Score of 4 assigned for change in nipple appearance (n=2), breast shape (n=2), and scar tissue formation (n=2)
Physician-reported assessment of overall breast cosmesis “good” or “excellent” for all patients

15. Conclusions
Proton PBI provides excellent early cancer control with acceptable cosmetic outcomes and minimal adverse effects as per patient- and physician-reported assessments
With continued follow-up, late toxicity and long term disease control outcomes will be assessed
Amendment in submission to IRB to increase enrollment to 138 patients

16. Acknowledgements Proton Collaborative Group (PCG) Protocol Chairs
Andrew L. Chang, MD – Study Chair
Carlos Vargas, MD – Co-Chair
Rashmi Benda, MD – Co-Chair
Wen Hsi, PhD - Physicist
Participating Sites
Hampton University Proton Therapy Institute (HUPTI)
ProCure PTC Oklahoma City
Northwestern Medicine Chicago Proton Center