PURPOSE / OBJECTIVE(s) RESULTS - PowerPoint Presentation

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PURPOSE / OBJECTIVE(s)

RESULTS

The use of proton therapy (PT) for partial breast irradiation (PBI) in early stage breast cancer is an area of active investigation. Proton PBI has the potential for decreased morbidity versus photon PBI because of superior sparing of surrounding normal breast tissue and underlying thoracic structures with protons. (Figure 1) To date, single-institutional studies have reported the feasibility of proton PBI but have resulted in conflicting results on toxicities, with some publications showing suboptimal cosmetic outcomes. (Table 1) Herein, we report 3-year outcomes of a prospective phase II trial investigating the efficacy, toxicity, and cosmetic outcomes of proton PBI.

Proton therapy is a safe and effective method of PBI delivery, with exceptional disease control, minimal toxicity, and acceptable patient- and physician-reported cosmesis and quality of life outcomes with longer-term follow-up. At 3 years, proton PBI provides 100% cancer control for early stage, ER-positive breast cancer. Acute toxicities are minimal, and patient-reported QOL remains acceptable with continued follow-up. Improvements in heart, lung, and nontarget breast tissue achieved with proton PBI compared with photon PBI may contribute to a decrease in clinically significant late toxicities such as major cardiovascular events, lung fibrosis, and secondary malignancy. This will need to be proven in longitudinal studies to quantify the true long-term clinical benefits of proton PBI.With continued refinement and optimization of proton PBI delivery and increase in patient access to proton therapy, this treatment approach will likely gain more widespread acceptance as the treatment that provides maximum benefit and minimum toxicity for selected patients with early stage breast cancer.

This was a multi-center Proton Collaborative Group phase II trial (PCG BRE 007-12).Inclusion criteria:Women ≥50 years of age AJCC stage 0-2, ≤3 cm, node negativeNonlobular invasive breast cancer or ductal carcinoma in situEstrogen receptor (ER)-positive disease Undergoing breast conservation therapy After breast conserving surgery, proton PBI was delivered to 40 Gy (RBE) in 10 fractions over 2 weeks.All patients received uniform scanning PT except 1 patient who received passively scattered PT.At least 2 treatment fields were used. Study primary endpoint was progression-free survival.Adverse events were prospectively graded using CTCAE version 4.0. The Breast Cancer Treatment Outcome Scale (BTCOS) was used to assess patient-reported quality of life (QOL) endpoints and cosmesis: 1=none 2=mild 3=moderate 4=large

Thirty-eight evaluable patients were enrolled between 2/2013-11/2016. Seventeen patients (45%) had right-sided disease; median tumor size was 0.95 cm. (Table 2) Median age was 67 years (range 50-79). Hormone therapy was administered in 29 of 38 patients (76.3%).

At a median follow-up of 35 months (range 12-62), all patients were alive, and no patient had local, locoregional or distant disease progression. One patient developed a new ER-negative invasive ductal carcinoma of the contralateral breast.

1. Kozak KR, Smith BL, Adams J, et al: Accelerated Partial Breast Irradiation Using Proton Beams: Initial Clinical Experience. Int J

Radiat

Oncol Biol Phys 2006:66:691-6982. Galland-Girodet S, Pashtan I, MacDonald SM, et al: Long-term Cosmetic Outcomes and Toxicities of Proton Beam Therapy Compared With Photon-Based 3-Dimensional Conformal Accelerated Partial-Breast Irradiation: A Phase 1 Trial. Int J Radiat Oncol Biol Phys 2014; 90:493-5003. Bush DA, Slater JD, Garberoglio, et al: Partial Breast Irradiation Delivered With Proton Beam: Results of a Phase II Trial. Clin Breast Cancer 2011;11:241-245 4. Bush DA, Do S, Lum S, et al: Partial Breast Radiation Therapy With Proton Beam: 5-Year Results With Cosmetic Outcomes. Int J Radiat Oncol Biol Phys 2014;90:501-5055. Chang JH, Lee JK, Kim JY, et al: Phase II Trial of Proton Beam Accelerated Partial Breast Irradiation in Breast Cancer. Radiother Oncol 2013;108:209-214

Seven grade 2 adverse events occurred:Radiation dermatitis (n=1, 2.6%)Lymphedema (n=1, 2.6%)Hot flashes (n=3, 7.9%)Dyspnea (n=1, 2.6%)Fatigue (n=1, 2.6%)No acute grade ≥3 acute or late toxicity attributable to radiotherapy were observed. Five patients (13%) assigned a BTCOS score of 4 at 1- or 3-year follow-up for change in nipple appearance (n=3), breast shape (n=4), scar tissue formation (n=2), breast texture (n=1) and bra fit (n=1). Dosimetric endpoints of interest:Heart V5Gy (median volume of the heart receiving 5 Gy) = 0%Lung V20Gy = 0% Lung V10Gy = 0.17%

SUMMARY / CONCLUSION

MATERIAL & METHODS

REFERENCES / ACKNOWLEDGEMENTS

Clinical Outcomes after Proton Partial Breast Radiotherapy for Early Stage- Hormone Receptor Positive Breast Cancer: 3-Year Outcomes of a Phase II TrialJ. I. Choi1, K. Prabhu Jr2, W. F. Hartsell3, C. C. Sinesi4, C. E. Vargas5,6, R. K. Benda7, O. Cahlon8, A. L. Chang91New York Proton Center, New York, NY, USA, 2ProCure Proton Therapy Center, Oklahoma City, OK, USA, 3Northwestern Medicine, Chicago Proton Center, Chicago, IL, USA, 4Hampton University Proton Therapy Institute, Hampton, VA, USA, 5Mayo Clinic, Scottsdale, AZ, USA, 6Department of Radiation Oncology, Mayo Clinic Arizona, Phoenix, AZ, 7Boca Raton Regional Hospital, Boca Raton, FL, USA, 8Memorial Sloan Kettering Cancer Center, New York, NY, USA, 9California Protons Cancer Therapy Center, San Diego, CA, USA

Isabelle Choi, MD New York Proton Center

ichoi@nyproton.com 225 East 126th Street, New York, NY 10035

Patient Characteristics

Median

Age67 years (50-79)Tumor Size0.95 cm (0.1-3.0)  LateralityNumber of patients (N)Right17Left21  Histology IDC only15DCIS only8Mixed IDC + DCIS12  Histologic Grade 11421935  Receptor StatusPositiveER100%PR100%HER211% (4/35)

Institution# PatientsDose/FxRadiation TherapyMD-Reported CosmesisPatient-Reported CosmesisToxicityDisease ControlMGH 19 PBT79 photon or photon-electron32 Gy (RBE) / 8 fx BID1-3 fields for PBT1.5-2 cm margin to PTV<5 mm from skin7yr: Good-excellent 62% PBT, 94% photon7yr: 92% PBT vs 96% photon, NSSTelangiectasias (PBT vs photon) 69% vs 16% (P=0.03)Pigmentation changes 54% vs 22% (P=0.02)Other late skin tox 62% vs 18% (P=0.029)7yr LF 11% PBT (n=3) vs 4% photon (n=2), NSSNCC, Korea 30 PBT30 Gy (RBE) / 5 fx QD1-2 fields PBT3yr: Good-excellent 69% (~100% with 2-field plan)--Increased toxicity with single field planNo LF or DFLLU 50 PBT40 Gy (RBE) / 10 fx QD2-4 fields PBT1 cm tumor bed margin to CTV5yr: Good-excellent 90% at 5 years5yr: Good-excellent 90%Acute: 62% grade 1-2 RT dermatitis; No grade 3 AELate: 7 cases of Gr 1 telangiectasia (7%); 1 pt with fat necrosisNo LF5yr OS 95%

Table 1. Proton partial breast irradiation studies.

Figure 1. Dose distribution using protons (left) and photons (right) for partial breast treatment of a left-sided lesion in the supine position. Beam arrangements include left lateral, anterior, and 2 axial oblique beams. Red contour: tumor bed. Blue contour: CTV.

Table 2: Patient Characteristics.