Accelerated Partial Breast Irradiation (APBI)

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Accelerated Partial Breast Irradiation (APBI) Michael Zhang (MSIV), Matthew Spraker, MD, PhD (PGY3) Faculty Mentor: Janice Kim, MD University of Washington/Seattle Cancer Care Alliance Seattle, WA

Case Presentation 62 year old female underwent annual bilateral screening mammogram A new focal asymmetry in the left breast upper outer quadrant was demonstrated Patient is otherwise asymptomatic

Patient History Past Medical History Hyperlipidemia Past Surgical History Tonsillectomy as a child C-section in 1984 Medications Atorvastatin No known drug allergies

Patient History (con t) Gynecologic History G2P3, 28 years old at first pregnancy Second pregnancy identical twins Menarche at 13, natural menopause at 50 OCP use from age 21-27, and hormone replacement therapy from age 52-54. Social History Currently working full time as an engineer. Never smoker, no current alcohol or drug use, or history of IV drug use. No prior XRT exposure. Strong family support. No known family history of malignancy

Physical Exam Vitals: HR 62, BP 117/75, RR 13, Temp 98.4F General: Well-appearing female, relaxed, alert, conversational. Lymphatics: No palpable cervical, supraclavicular, or axillary lymphadenopathy bilaterally. CV: RRR, no murmurs, rubs, or gallops. Resp: CTA B/L. Breast: Breasts are symmetrical and appear to be D cup breasts. There is no visible erythema, edema, nipple inversion, or discharge. There are no palpable masses. Neurologic: CN II-XII grossly intact, no focal neurologic deficits otherwise noted, sensation grossly intact throughout, gait normal.

Diagnostic Workup Diagnostic left mammogram Confirms 13mm irregular mass in the left breast at 1 o clock, mid-depth. Targeted US of left breast Re-demonstrates 13mm solid mass in the left breast at 1 o clock, 30mm from nipple. US-guided core needle biopsy Invasive ductal carcinoma Intermediate grade ER/PR positive (Allred 8/8 for both), Her2/neu amplification negative by FISH analysis.

Multidisciplinary Discussion Patient was presented at the multidisciplinary breast cancer tumor board. Presented options for local treatment: simple mastectomy, lumpectomy/slnb + WBI, or lumpectomy/slnb + accelerated partial breast irradiation (APBI). The patient elected to undergo lumpectomy/slnb + APBI using Contura multilumen balloon catheter.

Introduction to APBI Whole breast irradiation (WBI) Standard of care after breast conservation surgery for early stage breast cancer. APBI introduced with possible advantages over WBI while providing equivalent LC in low risk patients Shortened treatment course Typically 5-7 days vs 4-6 weeks Decreased radiation dose/toxicity Reduced exposure to heart, lung, ribs.

Which patients should be considered for APBI? Must be candidates for breast-conserving therapy No prior radiotherapy No history of collagen vascular diseases Not pregnant Consensus guidelines from ASTRO in 2009 put patients into 3 classes Suitable Cautionary Unsuitable

ASTRO consensus statement for APBI Suitable (Pt meets all criteria) Cautionary (Pt meets any criteria) Age 60 50-59 < 50 Unsuitable (Pt meets any criteria) Tumor Size, T stage 2 cm, T1 2.1 3 cm, T0 or T2 > 3 cm, T3-T4 N stage, surgery pn0 (SNBx or ALND) pn1-3 or no nodal surgery Margins Negative ( 2 mm) Close (< 2 mm) Positive LVSI No Limited/focal Extensive ER status Positive Negative Centricity Unicentric Microscopic multicentricity Histology Invasive ductal or favorable histology Invasive lobular Present EIC or Pure DCIS Not allowed 3 cm > 3 cm Associated LCIS Allowed Neoadjuvant Tx Not allowed Received

ASTRO vs. ABS vs. ASBS ASTRO Suitable (2009) ABS (2013) ASBS (2011) Age 60 50 45 (IDCA), 50 (DCIS) Tumor Size, T stage 2 cm, T1 3 cm 3 cm N stage, surgery pn0 (SNBx or ALND) pn0 (SNBx or ALN level I/II) pn0 (SNBx) Margins Negative ( 2 mm) Negative microscopic Negative microscopic Centricity Comparison of criteria for approved group Unicentric, clinically unifocal Unifocal LVSI Not present Not present Histology Invasive ductal or favorable histo Any invasive Invasive ductal or DCIS

APBI Methodology Multiple methods available Brachytherapy Multi-catheter interstitial (High, Low, or Pulsed dose rates) SAVI Balloon catheterization (Mammosite, Contura) External beam Electrons 3D-CRT/IMRT Protons Single-dose intraoperative radiotherapy (IORT) Multi-catheter interstitial brachytherapy has longest history, but currently data lacking to determine optimal method of delivering APBI.

RTOG 95-17 - Phase II trial APBI alone using multi-catheter interstitial brachytherapy after lumpectomy in early-stage breast cancer. 99 patients treated prospectively with HDR or LDR brachytherapy. Modality Eligibility: Stage I/II, unifocal, invasive non-lobular, negative margins, Tumor 3cm, Level I/II ALND with 0-3 positive nodes without ECE. HDR (34Gy, 10 BID fxns in 5 days) LDR (45Gy in 3.5-6 days) # pts tx Tumor Median control 5-year failure (Arthur rates 2008 IJROBP) f/u Ipsilat. br Contralat. br Regional Survival rates Mastectomy free Disease free Overall 66 6.55 yrs 3% 2% 5% 88% 86% 92% 33 7.09 yrs 6% 6% 0% 85% 88% 94%

RTOG 95-17 - Phase II trial (cont d) Toxicity and cosmesis (Rabinovitch et al. 2014) Skin toxicity at 5 years (% of pts): Grade 1-2 (78%), Grade 3 (13%), no G4 54% - Catheter marks 45% - Fibrosis 45% - Telangiectasias 37% - Dimpling or indentation 15% - Symptomatic fat necrosis (1 req d surgical excision, no pt req d mastectomy) Patient-reported outcomes after 5 years (% of pts): Breast asymmetry (73%), of which 77% reported a smaller treated breast Excellent/good cosmesis (66%) Satisfaction w/ treatment (75%) Would choose same treatment again (95%)

Treatment Our patient underwent lumpectomy/slnb with Contura maintenance catheter placement intraop Invasive ductal carcinoma measuring 7mm No associated DCIS Surgical resection margins widely negative (>5mm for all margins) ER+, PR+, Her2/neu amplification negative SLNBx reviewed intraoperatively 0/2 LNs positive for disease Contra balloon spacer replaced with Contura HDR brachytherapy unit during CT simulation

Treatment CT simulation completed with brachytherapy device in place. Pt is simulated on breast board with both arms up. Maintenance catheter was removed and Contura treatment catheter device placed with radioopaque dye to visualize balloon and intraluminal catheters for treatment planning. Treatment device remains in place for 5 days. Total dose of 34Gy delivered in BID fractions with greater than 6 hours of intrafx interval.

Treatment Five catheter channels connected to HDR after-loader for treatment

Treatment Set Up Catheter aligned to tattoo to ensure daily rotational consistency.

Fluoroscopic imaging to ensure set up performed prior to each daily fraction Day 1 Fluoroscopy set up Day 3 Fluoroscopy set up

References American Society of Breast Surgeons, 2011, https://www.breastsurgeons.org/statements/pdf_statements/apbi.pdf Arthur, D.W., Winter, K., Kuske, R.R., Bolton, J., Rabinovitch, R., White, J., Hanson, W.F., Wilenzick, R., and McCormick, B. (2008). A Phase II Trial of Brachytherapy Alone Following Lumpectomy for Select Breast Cancer: tumor control and survival outcomes of RTOG 95-17. Int. J. Radiat. Oncol. Biol. Phys. 72, 467 473. Kamrava, M., Kuske, R.R., Anderson, B., Chen, P., Hayes, J., Quiet, C., Wang, P.-C., Veruttipong, D., Snyder, M., and Jeffrey Demanes, D. (2015). Outcomes of Breast Cancer Patients Treated with Accelerated Partial Breast Irradiation Via Multicatheter Interstitial Brachytherapy: The Pooled Registry of Multicatheter Interstitial Sites (PROMIS) Experience. Ann. Surg. Oncol. Rabinovitch, R., Winter, K., Kuske, R., Bolton, J., Arthur, D., Scroggins, T., Vicini, F., McCormick, B., and White, J. (2014). RTOG 95-17, a Phase II trial to evaluate brachytherapy as the sole method of radiation therapy for Stage I and II breast carcinoma-- year-5 toxicity and cosmesis. Brachytherapy 13, 17 22. Shah, C., Vicini, F., Wazer, D.E., Arthur, D., and Patel, R.R. (2013). The American Brachytherapy Society consensus statement for accelerated partial breast irradiation. Brachytherapy 12, 267 277. Smith, B.D., Arthur, D.W., Buchholz, T.A., Haffty, B.G., Hahn, C.A., Hardenbergh, P.H., Julian, T.B., Marks, L.B., Todor, D.A., Vicini, F.A., et al. (2009). Accelerated partial breast irradiation consensus statement from the American Society for Radiation Oncology (ASTRO). Int. J. Radiat. Oncol. Biol. Phys. 74, 987 1001. Please provide feedback regarding this case or other ARROcases to arrocase@gmail.com