ROC Newsletter August 2013 New Clinical Trials Open for the Treatment of Breast Cancer with Proton Beam Therapy There is a large body of evidence suggesting an association between breast radiotherapy and a small, but significant risk of serious late toxicities including second malignancy and coronary artery disease. 1,2,3 In recent years, advances in the detection and treatment of breast cancer have resulted in improved long-term survival. As a result, issues of survivorship are of paramount importance. We are pleased to share with you that novel techniques for the treatment of both locally advanced and early stage breast cancer using proton beam therapy are now available at the Central DuPage Proton Center. Proton therapy has the potential to provide superior sparing of normal tissues adjacent to the breast or chest wall, including the heart, lung, and contralateral breast (Figure 1). BRE-008-12 A Phase II Study of Postoperative Cardiac-Sparing Proton Radiotherapy for Women with Stage III, Loco-regional, Non-metastatic Breast Cancer Comprehensive locoregional therapy to the breast or chest wall and regional lymphatics following definitive surgery for patients with locally advanced disease improves breast cancer outcomes. 4,5 However, full regional coverage comes at the expense of increased dose to normal tissues and risk of acute and late toxicity. 6 Preliminary dosimetric and clinical studies have demonstrated that proton therapy can provide substantial improvements in target coverage, dose homogeneity, and normal tissue sparing in cases where comprehensive nodal irradiation (including the internal mammary chain) is clinically indicated. 7,8 The ability to limit heart dose, and more specifically coronary artery dose, may be particularly important in patients exposed to cardiotoxic chemotherapy (e.g. adriamycin, traztuzumab) or with pre-existing cardiovascular comorbidities.
Figure 1: Comparison plans for treatment of the chest wall and regional lymphatics after mastectomy and implant-based reconstruction for a patient with Stage III breast cancer (a). Images depict color-washed doses ranging from 5% to 105% of the prescription. Using a partially wide photon tangent technique, the heart, lung, and contralateral breast receive significant radiation dose. With proton planning (b), the dose distribution provides full target coverage while sparing more normal tissue. In a patient with an intact breast, employing a shallow photon tangent with matched electron field (c) results in unwanted dose to heart and lungs. A proton plan is able to avoid these tissues (d). In the setting of right-sided breast cancers, protons can also provide a significant benefit (e, f). PHOTONS PROTONS (a) (b) (c) (d) (e) (f)
The BRE-008 trial is designed to determine rates of acute and long term adverse events associated with postoperative proton radiotherapy for complex locoregional irradiation in women with locally advanced breast cancers. The trial will also examine dosimetric comparisons of proton and conventional radiation plans. Disease outcomes including local, regional, and distant control and overall survival will be documented. Treatment Schema: Volume Definition: Target delineation for the breast, chest wall, axilla, supraclavicular region, and internal mammary chain will follow Radiation Therapy Oncology Group (RTOG) consensus guidelines. Prescription Dose: 50.4 CGE in 1.8 CGE once daily fractions over 28 sequential treatment days will be delivered to the breast or chest wall and to the regional lymphatics. A 10.8 CGE lumpectomy cavity boost will be delivered. Chest wall scar boost is optional. Clinically positive internal mammary nodes will receive an additional 10.8-16.2 CGE. Treatment Planning: A dedicated triple contrast cardiac CT will be acquired and fused to the treatment planning CT for delineation of coronary arteries. Beam arrangement will be individualized based on patient anatomy. The chest wall will be treated with perpendicularly oriented beams to limit the dosimetric impact of respiratory motion. Image Guidance: Daily orthogonal kv images will be acquired to ensure accuracy of setup and treatment delivery. Eligibility Criteria: Stage III Breast Cancer (AJCC 7 th edition) Right or Left Breast (bilateral breast cancer excluded) Life expectancy 10 years Female age 18 years Negative Margins Treatment to begin within 9 weeks post-operatively OR within 2 to 8 weeks after last cycle chemotherapy Technical Considerations: Tissue expanders containing metallic ports interfere with proton beam treatments. In patients undergoing immediate reconstruction, metalcontaining tissue expanders should be exchanged for permanent implants. Patient anatomy may preclude technical feasibility (i.e very large, pendulous breasts which limit daily set-up reproducibility)
BRE-007-12 A Phase II Protocol of Proton Therapy for Partial Breast Irradiation in Early Stage Breast Cancer Prospective, non-randomized studies have demonstrated the safety and efficacy of partial breast irradiation for select patients with early stage breast cancer. 9,10 Several techniques are available to deliver partial breast treatment, including brachytherapy, in which a catheter or balloon is surgically inserted into the lumpectomy cavity, as well as conventional external beam radiation. One promising alternative to currently available techniques is that of proton therapy. Proton partial breast irradiation offers several potential advantages over conventional external beam radiation or brachytherapy. 11 First, it is non-invasive, and therefore suitable for patients at high risk for infection or poor wound healing. Furthermore, there is a potential to reduce dose to normal surrounding tissues including heart, lung, and uninvolved breast tissue compared to other techniques. 12 (see Figure 2) Figure 2: Axial (a), sagittal (b), and coronal (c) sections of a partial breast irradiation plan for an invasive ductal carcinoma (pt1an0) in the lower-central region of the left breast. Isodose lines ranging from 10% to 105% of the prescription dose are depicted demonstrating sparing of heart and lung tissue. For this plan, the heart V5 is 0.01% and mean heart dose 1 cgy. Left lung mean dose is 9 cgy and V5 is <1%. Overall hot spot 107%. (a) (b) (c)
The BRE-007-12 trial is designed to determine disease control rates and acute and long-term toxicity of partial breast irradiation using proton therapy for the treatment of early stage breast cancer. Treatment Schema: Prescription Dose: 40 CGE in 4 CGE daily fractions over 10 sequential treatment days. Treatment Planning: A minimum of 3 fields will be employed to limit skin dose. Image Guidance: Surgical clips will be used as fiducials to ensure accurate patient setup. If no clips were placed at the time of lumpectomy, placement of radio-opaque markers in the breast within 6 weeks post-operatively is required. Eligibility Criteria: In situ or invasive ductal carcinoma (lobular histology not allowed) Stage 0, I, or II with tumor size 3 cm Age 50 Unifocal Margins >2mm pn0 by sentinel node biopsy or axillary node dissection ER Positive Oncotype score documented (all scores eligible) Please direct questions regarding proton therapy for breast cancer or clinical trial enrollment to: Corey Woods, RN corey.woods@chi.procure.com (630) 821-6397 OR Paige Dorn, MD (630) 352-5350 pdorn@chicagocancer.org
References 1 Darby SC, Ewertz M, McGale P, et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. New Engl J Med 2013, March 14; 368 (11): 987-98. 2 Rubino C, Shamsaldin A, Le MG, et al. Radiation dose and risk of soft tissue and bone sarcoma after breast cancer treatment. Breast Cancer Res Treat. 2005; 89:277-288. 3 Nilsson G, Holmberg L, Garmo H, et al. Distribution of coronary artery stenosis after radiation for breast cancer. J Clin Oncol. 2011; 30(4):380-386. 4 Ragaz J, Olivotto IA, Spinelli JJ, et al. Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial. J Natl Cancer Inst 2005, 97:116 126. 5 Whelan TJ, Olivotto IA, Ackerman I.et al. NCIC-CTG-MA.20: an intergroup trial of regional nodal irradiation in early breast cancer. J Clin Oncol 2011; 29:80s (suppl; abstr LBA504). 6 Deutsch M, Land SR, Begovic M, et al. The incidence of lung carcinoma after surgery for breast carcinoma with and without postoperative radiotherapy: results of National Surgical Breast and Bowel Project (NSABP) clinical trials B-04 and B-06. Cancer. 2003; 98(7): 1362-1368. 7 Ares C, Khan S, MacArtain AM, et al. Postoperative proton therapy for localized and locoregional breast cancer: potential for clinically relevant improvements? Int J Radiat Oncol Biol Phys. 2010; 76(3):685-697. 8 MacDonald SM, Jimenez R, Paetzold, et al. Proton radiotherapy for chest wall and regional lymphatic radiation; dose comparisons and treatment delivery. Radiation Oncology 2013; 8:71. 9 Beitsch PD, Wilkinson JB, Vicini FA, et al. Tumor bed control with balloon-based accelerated partial breast irradiation: incidence of true recurrences versus elsewhere failures in the American Society of Breast Surgery MammoSite( ) Registry Trial. Ann Surg Oncol. 2012 Oct;19(10):3165-70. 10 Lei RY, Leonard CE, Howell KT,et al. Four-year clinical update from a prospective trial of accelerated partial breast intensity-modulated radiotherapy (APBIMRT). Breast Cancer Res Treat. 2013 Jul;140(1):119-33. 11 Bush DA, Slater JD, Garberoglio C, et al. Partial breast irradiation delivered with proton beam: results of a phase II trial. Clin Breast Cancer 2011; 11 (4): 241-245. 12 Moon SH, Shin KH, Kin TH, et al Dosimetric comparison of four different external beam partial breast irradiation techniques.