Accelerated Partial Breast Irradiation (APBI) Michael Zhang (MSIV), - PowerPoint PPT Presentation

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 November 16, 2015

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 multi- lumen balloon catheter. November 16, 2015

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. November 16, 2015

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 November 16, 2015

ASTRO consensus statement for APBI Suitable Cautionary Unsuitable (Pt meets all criteria) (Pt meets any criteria) (Pt meets any criteria) Age ≥ 60 50-59 < 50 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 multi- Present centricity Histology Invasive ductal or Invasive lobular favorable histology EIC or Pure DCIS Not allowed ≤ 3 cm > 3 cm Associated LCIS Allowed Neoadjuvant Tx Not allowed Received November 16, 2015

ASTRO vs. ABS vs. ASBS Comparison of criteria for approved group ASTRO “Suitable” ABS (2013) ASBS (2011) (2009) 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 pN0 (SNBx) level I/II) Margins Negative (≤ 2 mm) Negative microscopic Negative microscopic Centricity Unicentric, clinically Unifocal unifocal LVSI Not present Not present Histology Invasive ductal or Any invasive Invasive ductal or DCIS favorable histo November 16, 2015

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. November 16, 2015

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. – Eligibility: Stage I/II, unifocal, invasive non-lobular, negative margins, Tumor ≤3cm, Level I/II ALND with 0 -3 positive nodes without ECE. Tumor control (Arthur 2008 IJROBP) Modality # pts Median 5-year failure rates Survival rates tx f/u Ipsilat. Contralat. Regional Mastectomy Disease Overall br br free free HDR 66 6.55 yrs 3% 2% 5% 88% 86% 92% ( 34Gy, 10 BID fxns in 5 days) LDR 33 7.09 yrs 6% 6% 0% 85% 88% 94% ( 45Gy in 3.5-6 days) November 16, 2015

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%) November 16, 2015

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 radio- opaque 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 November 16, 2015

Treatment Set Up Catheter aligned to tattoo to ensure daily rotational consistency. November 16, 2015

Fluoroscopic imaging to ensure set up performed prior to each daily fraction Day 1 – Fluoroscopy set up Day 3 – Fluoroscopy set up November 16, 2015

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 November 16, 2015