1. INTRAOPERATIVE RADIATION THERAPY (IORT) for EARLY-STAGE BREAST CANCER Dr. Maria C.E. Jacobs Director, Radiation Oncology Mercy Medical Center Baltimore, Maryland

2. EARLY-STAGE BREAST: Local Breast Treatment
BCT consisting of conservative surgery (CS) with lumpectomy/partial mastectomy and RT
Mastectomy +/- immediate reconstruction

3. BREAST CONSERVATION THERAPY: Treatment Objectives
Optimize local control
Minimize acute and long-term complications
Maintain optimal cosmesis

4. Breast Conservation Therapy (BCT) is a standard of care supported by years of data.
BCT refers to breast-conserving surgery (BCS) + radiotherapy.
27+ years of data support BCT as a standard of care.
Six modern, prospective randomized trials found no significant differences when comparing BCT to mastectomy.
Clinical trials compared local recurrence, distant metastasis, and long-term survival.
During the past two decades, breast-conserving therapy—lumpectomy followed by radiation therapy—has become the standard of care for the treatment of early-stage breast cancer. Breast conservation therapy was originally investigated as an alternative to mastectomy to allow a woman to preserve her breast. Multiple studies have shown that breast- conserving treatment achieves rates of local control that are equivalent to mastectomy, while providing superior cosmetic results.
We now have over 27 years of data supporting breast-conserving therapy as the standard of care for early-stage invasive breast cancer. Six major trials have proven that there is no significant difference between BCT and mastectomy in terms of local recurrence, distant metastasis and survival. Most of these clinical trials have now published long-term follow-up results.

5. RANDOMIZED TRIALS COMPARING MASTECTOMY vs. BCT
NCI (Milan)
NSABP B-06
NCI (France)
NCI (USA)
EORTC
Danish Group

6. Prospective Randomized Trials comparing Mastectomy (M) vs. BCT
Trial No. of Pts %Local Recurrence %Survival F/U Interval
BCT M BCT M (YR)
NASBP
MILAN
NCI
EORTC
IGR
DBCG

7. Summary of Randomized Trials: BCT vs. Mastectomy
Continuous follow-up demonstrates NO significant differences between BCT and mastectomy in:
- loco-regional control
- distant metastases
- overall survival
No disadvantage in the use of BCT for patients with positive axillary lymph nodes
No significant differences in the rate of second malignancies or contralateral breast cancer

8. Critical Elements in the Selection of Patients for BCT
History and Physical Exam:
- Age should not be a contraindication for BCT
- Comorbid conditions should be considered prior to BCT
- Locally-advanced disease
Radiological Evaluation:
- Multicentricity
- Extent of calcifications

9. Critical Elements in the Selection of Patients for BCT
Pathologic Evaluation:
- Positive axillary lymph nodes are NOT a contraindication for BCT
- NEGATIVE margins of resection
Needs and Expectations:
- Self-esteem/Sexuality
- Sense of disease control
- Functionality
- Overall quality of life

10. Contraindications for BCT
Absolute:
- More than two primaries in separate quadrants
- Diffuse and pleomorphic calcifications
- History of previous RT to the breast
- Pregnancy in the first and second trimesters Surgery can be performed in third trimester and RT can be deferred until after delivery
- Persistent positive margins of resection after “reasonable” surgical attempts

11. Contraindications for BCT
Relative:
- History of collagen vascular disease. Scleroderma and active systemic lupus are ABSOLUTE contraindications
- Large tumor in small breast
- Large and pendulous breast preventing daily reproducibility and dose homogeneity

12. Non-Mitigating Factors in the Selection of Patients for BCT (factors not affecting acceptability)
Family history of breast cancer is NOT a contraindication for BCT
BRCA 1 and 2 mutations are NOT a contraindication for BCT
High risk for systemic relapse is NOT a contraindication for BCT. It is a determinant
for adjuvant systemic management
BCT can be offered to patients with positive axillary lymph nodes

13. Radiation Therapy for Early-Stage Breast Cancer (post-lumpectomy)
Whole Breast Irradiation for centiGray in daily fractions of centiGray/fraction
Tangential fields, 6-18 MV photon beam
“Boost” for centiGray in 8-10 fractions using an electron beam or “mini-tangential fields depending on tumor bed depth

14. Standard Breast Irradiation: Side Effects and Long-Term Complications
Acute
- Skin: discoloration, dry and moist desquamation
- Fatigue
- Anemia is rare
Long-Term
- Arm and breast edema
- Myositis
- Pneumonitis

15. Under-Utilization of BCT
240,000 Breast Cancer Cases in 20071
~180,000 Eligible for Breast Conservation Therapy (BCT)2 a
~72,153
40%
~73,957
41%
Mastectomy
BCT
So although BCT is equivalent to mastectomy in terms of recurrence and survival rates, it is still very underutilized. At a 1990 Conference sponsored by the National Institutes of Health, experts agreed that since survival rates were the same, lumpectomy followed by radiation is the preferable treatment for most women with early-stage breast cancer4. But even today, more than 15 years later, many women eligible for breast-conserving surgery are getting mastectomies.
In 2007, upwards of 180,000 women will be eligible for breast conservation therapy. However, according to SEER data, only about 40% of eligible women receive BCT each year. Another 41% receive mastectomy and 19% get a lumpectomy without follow-up radiation therapy. In 2007, this means that over 108,000 women may not receive the preferred method of treatment for their early-stage breast cancer. And sadly, over 34,000 are risking recurrence by not having their recommended course of radiation therapy.
An idea behind MammoSite Targeted Radiation Therapy and other forms of APBI is that this treatment modality can help increase the number of women who receive breast conservation therapy and help reduce the numbers of women who receive mastectomy and lumpectomy only.
2007 Cancer Facts & Figures American Cancer Society.
U.S. Department of Health and Human Services, Office on Women’s Health.
SEER Data Incidence Rates, NCI.
The National Institutes of Health Consensus Statement on Treatment of Early-Stage Breast Cancer states: “Breast Conservation Surgery plus radiotherapy is preferable to total mastectomy because it provides survival equivalence while preserving the breast.” (Consensus statement on treatment of early-stage breast cancer. National Institutes of Health, 1992).
Lumpectomy
No Radiation
108,2303
Receive BCT Lumpectomy + WBRT or APBI
~34,273
19%
No Radiation
Eligible for lumpectomy but receive mastectomy
Receive BCS w/o Radiation
Source: Cancer Facts & Figures American Cancer Society
2U.S. Department of Health and Human Services, Office on Women’s Health
3SEER Data Incidence Rates, NCI

16. Women Eligible for Breast Conservation Therapy
41% mastectomies1
Reasons cited:2
- Time commitment
- Inconvenience
- Fear of radiation
- Treating physician bias
19% lumpectomy w/o radiation.1
Reasons cited:3
- Limited radiotherapy resources
- Treatment-related morbidity
- Loss of income due to prolonged
treatment duration with radiation
46% with DCIS have lumpectomy alone.4
Causative factors associated with under-treatment include issues with transportation, insurance coverage, employment and physical limitations.5
When you look at the reasons why women who are eligible for breast conservation therapy have mastectomies – or have lumpectomy and forgo the recommended course of radiation treatment – you see a pattern. Time commitment, loss of income, inconvenience and employment are all problems cited here that may be reduced with an accelerated treatment method. Five days of treatment versus 5-7 weeks makes receiving the recommended course of radiotherapy possible for many more women.
1. Cancer Trends Progress Report Update, National Cancer Institute, NIH, DHHS, Bethesda, MD, December 2005,
2. Keisch ME. Accelerated partial breast irradiation: the case for current use. Breast Cancer Res. 2005;7:
3. Vinh-Hung V, Verschraegen C. Breast-conserving surgery with or without radiotherapy: pooled-analysis for risks of ipsilateral breast tumor recurrence and mortality. J Natl Cancer Inst. 2004;96:
4. Baxter NN, Virnig BA, Durham SB, Tuttle TM. Trends in the treatment of ductal carcinoma in situ of the breast. J Natl Cancer Inst. 2004;96:
5. Jeruss JS, Vicini FA, Beitsch PD, et al. Initial outcomes for patients treated on the American Society of Breast Surgeons MammoSite clinical trial for ductal carcinoma-in-situ of the breast. Ann Surg Oncol. 2006;13:
1Cancer Trends Progress Report Update, National Cancer Institute, NIH, DHHS, Bethesda, MD, December 2005, 2Keisch ME. Breast Cancer Res. 2005;7: Vinh-Hung et al. J Nat Cancer Inst. 2004:96: Baxter et al. J Natl Cancer Inst. 2004;96: Jeruss et al. Ann Surg Oncol. 2006;13:

17. Is it Safe to Omit Radiation Therapy After BCS?
Several randomized trials have been conducted to determine if radiation therapy (RT) can be omitted after breast-conserving surgery.
No subset of patients has been identified that can conclusively be treated with surgery alone.
More recent efforts have investigated whether or not some patients could skip the radiation therapy and be treated with lumpectomy only, but the answer is no. Several studies have looked at this question, but no subset of patients that can safely skip radiation therapy has been identified.
1. Baxter NN, Virnig BA, Durham SB, Tuttle TM. Trends in the treatment of ductal carcinoma in situ of the breast. J Natl Cancer Inst. 2004;96:
2. Burstein HJ, Polyak K, Wong JS, et al. Ductal carcinoma in situ of the breast. N Engl J Med ;350:
3. Houghton J, George WD, Cuzick J, et al. Radiotherapy and tamoxifen in women with completely excised ductal carcinoma in situ of the breast in the UK, Australia, and New Zealand: randomised controlled trial. Lancet. 2003;362:
4. Julien JP, Bijker N, Fentiman IS, et al. Radiotherapy in breast-conserving treatment for ductal carcinoma in situ: first results of the EORTC randomised phase III trial EORTC Breast Cancer Cooperative Group and EORTC Radiotherapy Group. Lancet. 2000;355:
5. Fisher B, Costantino J, Redmond C, et al. Lumpectomy compared with lumpectomy and radiation therapy for the treatment of intraductal breast cancer. N Engl J Med ;328:
1 Baxter et al. J Natl Cancer Inst. 2004;96:
2 Burstein et al. N Engl J Med. 2004;350:
3 Houghton et al. Lancet. 2003;362:
4 Julien et al. Lancet. 2000;355:
5 Fisher et al. N Engl J Med. 1993;328:

18. Is Excision Alone Adequate in Any Subset of Patients
According to previous clinical trials, all subsets of patients benefit from RT
Risk factors for local recurrence after lumpectomy alone include tumor size, margins, grade, EIC and receptor status
A very selected group of patients may not require RT
RT is still STANDARD following CS

19. CS vs. CS AND RT for Early-Stage Breast Cancer: Impact of RT
Trial % Local Recurrence %Reduction (Recurrence)
CS CS+RT CS vs. CS+RT
NSABP
Ontario
Milan
Scottish
English
Uppsala-Orebro

20. Prospective Trials comparing CS vs. CS and RT
These trials have variables including extent of the surgical resection (wide excision vs. quadrantectomy) and length of follow-up
However, they all show a substantial reduction in the local recurrence rate with the addition of radiotherapy

21. Is Excision Alone Adequate in Any Subset of Patients
According to previous clinical trials, all subsets of patients benefit from RT
Risk factors for local recurrence after lumpectomy alone include tumor size, margins, grade, EIC and receptor status
A very selected group of patients may not require RT
RT is still STANDARD following CS

22. New/Alternative Treatment Approaches
Is excision alone adequate therapy?
Is the “boost” necessary?
Is partial breast irradiation an acceptable treatment modality?
Is accelerated partial breast irradiation (APBI) an acceptable option?

23. How Did the Concept of Accelerated Partial Breast Irradiation Originate?
Findings suggest that the major benefit of radiation therapy is derived from radiation directed at the breast tissue immediately surrounding the lumpectomy site.1
The majority of local recurrences after breast-conserving therapy occur at or near the tumor bed.1
The incidence of “elsewhere” failures appears to be unaffected by whole breast irradiation: 1-5% of patients fail elsewhere regardless of radiation.1,2
Whole breast irradiation may not be needed in appropriately selected patients.2
Several issues fostered the investigation of partial breast irradiation. We know that the majority of local recurrences occur at or near the tumor bed. We also know that studies suggest that the major benefit of radiation therapy is to the tumor bed immediately surrounding the lumpectomy site.
To date, whole breast radiation has been a standard of care, but when we look at the incidence of “elsewhere” failures, there appears to be little difference between patients who receive whole breast radiation therapy vs. patients who receive no radiation therapy, with a less than 3.8% rate of elsewhere failures regardless of radiation. So WBRT may not be necessary for appropriately-selected patients.
King TA, Bolton JS, Kuske RR, Fuhrman GM, et al. Long-term results of wide-field brachytherapy as the sole method of radiation therapy after segmental mastectomy for T(is,1,2) breast cancer. Am J Surg. 2000;180:
2. Arthur DW, et al. Accelerated partial breast irradiation: an updated report from the American Brachytherapy Society. Brachytherapy. 2002;1:
1King et al. Am J Surg. 2000;180:
2Arthur et al. Brachytherapy. 2002;1:

24. “Elsewhere” Failures
Incidence of failures outside of tumor bed in randomized trials comparing lumpectomy with or without postoperative irradiation.1
The data suggest WBRT does not protect against new disease development elsewhere in the breast.
Surgery Alone
Surgery Plus RT
Trial
Median f/u (mo) N %
NSABP-B06
125
17 / 636
2.7
24/629
3.8
Milan 39
4 / 273
1.5
0/294
Ontario 43
15 / 421
3.5
4/416
1.0
116 -
27/974
2.8
Several studies suggest that the incidence of “elsewhere” failures is unaffected by treatment with whole breast radiation therapy. In other words, WBRT offers no prophylactic protection against disease development elsewhere in the breast.
Baglan KL, Martinez AA, Frazier RC, et al. The use of high-dose-rate brachytherapy alone after lumpectomy in patients with early-stage breast cancer treated with breast-conserving therapy. Int J Radiat Oncol Biol Phys. 2001;50:
1Baglan et al. Int J Radiat Oncol Biol Phys. 2001;50:

25. Disease Extension Illustrated
Imamura
40-64
>64
100% ISO
75% ISO
100% ISO
Ohtake
≥50
75% ISO
These illustrations show the extension of disease in each age group. The red line is an illustration of the MammoSite Radiation Prescription Depth – 1 cm at 100% isodose. The green line is the 75% isodose. As you can see the Isodose covers the area of concern and beyond.
1. Imamura H, Haga S, Shimizu T, et al. Relationship between the morpCytycal and biological characteristics of intraductal components accompanying invasive ductal breast carcinoma and patient age. Breast Cancer Res Treat. 2000;62:
2. Ohtake T, Abe R, Kimijima I, et al. Intraductal extension of primary invasive breast carcinoma treated by breast-conservative surgery. Computer graphic three-dimensional reconstruction of the mammary duct-lobular systems. Cancer. 1995;76:32-45.
Imamura1: Max 8.32 mm
Ohtake2: Max 7.7 mm
Red Line is MammoSite Radiation Prescription Depth at 100% Isodose: 1 cm. Green line is 75% Isodose.
1Imamura et al. Breast Cancer Res Treat. 2000;62:
2Ohtake et al. Cancer. 1995;76:32-45.

26. Accelerated Fractionation Schedules: Partial Breast Irradiation
Brachytherapy
External Beam Radiotherapy
Intraoperative Radiotherapy

27. APBI Techniques External Beam for APBI CONTURA MammoSite
I summarize the APBI techs talked above, they are external x-ray irradiation, interstitial, MammoSite, Contura, and SAVI.
I mainly want to tell the difference between SAVI and MammoSite or Contura.
MammoSite
Interstitial multi-catheter
SAVI

28. Breast Brachytherapy Scientific Rationale
Published data reports low local recurrence rates, ranging from %,
in patients treated with brachytherapy as primary treatment.

29. Interstitial Brachytherapy – Multi-Entry/Multi-Catheter
The longest, most extensive follow-up APBI technique is the multicatheter, interstitial brachytherapy approach. With this approach, after-loading catheters are placed through the breast tissue surrounding the lumpectomy cavity. In general any shape can be covered by this method. It is, however, challenged by several facts, including the complexity of the procedure with multiple entry and operator dependence.
Arthur and Vicini, 2005

30. Published Data on Breast Brachytherapy as Primary Treatment: > 5-year Median Follow-up
Institution
# Patients
Follow-Up
% Local Recurrence
Ochsner Clinic1 New Orleans, Louisiana 51 75
2.0
William Beaumont Hospital2
199 72
1.1
National Institute Oncology3
128 66
4.7
Totals
378 70
2.4%
The longest term data on APBI is with the Multi-Catheter Interstitial Experience. In these multi-catheter studies that have longer-term follow-up -- more than five years -- you can see that the recurrence rate remains low, ranging from 1.1 to 4.7%. Data would suggest that five years is a key milestone.
1. King TA, Bolton, JS, Kuske, RR, et al. Long-term results of wide-field brachytherapy as the sole method of radiation therapy after segmental mastectomy for T(is,1,2) breast cancer. Am J Surg ;180:
2. Vicini F, Kestin L, et al. Limited-field radiation therapy in the management of early-stage breast cancer. J Natl Cancer Inst. 2003;95:
3. Polgar C, Fodor J, Major T, et al. Breast-conserving treatment with partial or whole breast irradiation for low-risk invasive breast carcinoma-5-year results of a randomized trial. Int J Radiat Oncol Biol Phys. 2007;69:
1 King et al. Am J Surg. 2000;180: Vicini et al. JNCI. 2003;95: Polgar et al. Int J Radiat Oncol Biol Phys. 2007;69:

31. William Beaumont Hospital Trial: Cosmetic Outcomes with APBI1
Population: 199 consecutive patients with invasive early-stage (I–II) breast carcinoma.
Treatment: Hypofractionated APBI using interstitial brachytherapy directed only at the region of the tumor bed.
Cosmetic Outcome
<6 months
2 years
>5 years
Excellent
10%
29%
33%
Good
85%
68%
66%
Fair 1% 2%
Total (Good + Excellent)
95%
97%
99%
Chen et al. conducted a prospective study at William Beaumont Hospital of accelerated partial breast irradiation (APBI) in women with invasive early-stage breast carcinoma. 199 women with stage I to II cancer were treated with APBI using interstitial brachytherapy directed only at the region of the tumor bed. All study participants had undergone macroscopic total resection of the primary tumor.
The cosmetic outcomes were never less than 95% for good-to-excellent scores. Note that the percentage of excellent scores increased over time. Nearly all (99%) of the women achieved good or excellent cosmetic results after a five-year interval.
Chen PY, Vicini FA, Benitez P, et al. Long-term cosmetic results and toxicity after accelerated partial breast irradiation: a method of radiation delivery by interstitial brachytherapy for the treatment of early-stage breast carcinoma. Cancer. 2006;106:
1Chen et al. Cancer. 2006;106(5):

32. Dosimetry Publication:
MammoSite Rationale
2002 IJROBP MammoSite
Dosimetry Publication:
Presents dosimetric characteristics of MammoSite
Analysis by William Beaumont, leader in breast brachytherapy
Key findings comparing MammoSite to multicatheter interstitial brachytherapy:
- Favorable volume coverage and reproducibility
Peer reviewed MammoSite dosimetry article
Although multicatheter breast brachy has shown good long term outcomes, this article demonstrates improvement of coverage and reproducibility with MammoSite over multicatheter breast brachy (evaluation based on Frank Vicini multicath dosimetry).
Dosimetric Characteristics of multicath interstitial are Coverage: D90 = 69.8% and Reproducibility: D90 Range = 61.1% %

33. MammoSite – Single Entry/Single Catheter
MammoSite is a balloon-catheter treatment device designed to simplify the brachytherapy procedure while improving the reproducibility of the dosimetric coverage of the clinic target. For Every treatment the balloon geometry, skin distance, and air cavity if any, all need to be checked as you know the symmetry tolerance is 2 mm and the air volume should be less than 10% of the PTV. That limits the use for MammoSite.
Arthur and Vicini, 2005

34. Contura Applicator- Single Entry/Multi-Catheter Balloon MammoSite
PTV for Contura
Contura breast applicator has a total 5 catheters: there are 4 catheters surrounding the central catheter. Contura is an improved MammoSite by view of dose distribution. Balloon geometry and symmetry can be beyond 2mm limitation.
Balloon
MammoSite

35. SAVI Applicator – Single Entry/Multi-Catheter
The strut-adjusted volume implant, SAVI, (Cianna Medical, Aliso Viejo, California) is recently developed and has been found combined advantages of both approaches mentioned above with a single entry of multicatheter device for APBI. Scanderbeg et al[26] at University of Colifornia, San Diego have reported clinic results of 20 patients treated with SAVI till SAVI uses multicatheters in the central and peripheral struts expandable and retractable to optimize tumor bed dose while minimizing normal tissue dose. A main advantage is the dose conformation to the patient-specific anatomy to cover the target and spare the surrounding normal structures.

36. ABS and ASBS Patient Selection Criteria
ABS Recommendations1
(updated February 2007)
ASBS Recommendations2 (updated December 2005)
Age
Diagnosis
Tumor Size
Surgical Margins
Nodal Status
≥ 50
≥ 45
Infiltrating ductal carcinoma
Invasive ductal carcinoma or DCIS
≤ 3 cm
≤ 3 cm
The current ABS and ASBS criteria are listed in this chart. One primary aim of these criteria is to select those patients who are at low risk for having disease elsewhere in the breast. Obviously, this is because partial breast treatment is directed only at the tissue immediately surrounding the lumpectomy cavity.
By these guidelines, those who are less likely to have multicentric disease and more likely to benefit from PBI are older women 45 and up for the ASBS and 50 and up for ABS. The ASBS includes those with DCIS or invasive ductal carcinoma, whereas the ABS guidelines include only infiltrating ductal carcinoma. Both guidelines agree on a tumor size of 3 cm or smaller, negative microscopic surgical margins and no positive nodes.
American Brachytherapy Society, Breast Brachytherapy Task Group paper. February Available at:
Consensus statement for accelerated partial breast irradiation. The American Society of Breast Surgeons. December 08, Available at:
Negative microscopic surgical margins of excision
Negative microscopic surgical margins of excision NØ NØ
1American Brachytherapy Society, Breast Brachytherapy Task Group, February 2007.
2Consensus statement for accelerated partial breast irradiation. American Society of Breast Surgeons, 2005.

37. NSABP B-39 /RTOG 0413: Phase III Trial
ABS Recommendations (Updated February 2007)
ASBS Recommendations (Updated December 2005)
*NSABP B39 - RTOG 0413 Eligibility Criteria
Age
>50
>45
>18
Diagnosis
Infiltrating ductal carcinoma
Invasive ductal carcinoma or DCIS
Invasive adenocarcinoma or DCIS
Tumor size
<3cm
Surgical margins
Negative microscopic surgical margins of excision
Negative microscopic surgical margins of excision by NSABP definition
Nodal status NØ
NØ; N1 (1-3 nodes)
Here are the inclusion criteria for the current Phase III trial. Accrual was closed earlier this year to lower risk patients. Patients over age 50 now must be either node positive or ER negative.
*NSABP B-39 enrollment now closed to lower risk patients: DCIS patients ≥ 50 years AND Invasive Breast Cancer patients ≥ 50 years who are node negative and hormone-receptor positive.

38. ACCELERATED PARTIAL BREAST IRRATDIATON
Reduction of treatment time from 6-7 weeks to 5 days
It decreases the target volume (lumpectomy plus 1-2 cm margin
Increases dose per fraction: 340 cGy twice daily (BID) x 5 days= 3,400 cGy
Use highly conformal dose delivery using CT based 3D-CRT

39. Lessons learned from APBI
Patient Appeal
Decreased Overall Treatment Time:
Radiotherapy: 1 week vs. 6-7 weeks
CS--chemotherapy (4-6 months)--RT(6-7weeks)
VS.
CS RT (1 week) Chemotherapy
Less skin toxicity
Less systemic toxicity

40. INTRAOPERATIVE RADIATION THERAPY (IORT): DEFINITION
Intraoperative Radiation Therapy (IORT) is the delivery of a single high dose of radiation to the target area/tumor bed at the time of surgery.

41. IORT
It is TRULY a multidisciplinary approach during which the surgeon removes the tumor and the radiation oncologist directs the radiation to the tumor bed, with both physicians working together, hand in hand, to spare surrounding normal tissues.

42. IORT
IORT is NOT a new approach to cancer management. As the result of pioneering work by Dr. Abe in Kyoto, Japan, IORT using linear accelerators has been used in the U.S.A., Europe and Japan for the treatment of malignancies in the abdomen (sarcomas, rectum, gynecologic and retroperitoneal tumors)

43. IORT: History
1909: Beck treated a patient with colon cancer using low-energy X-rays
Early 1970, Dr. Abe in University of Kyoto, Japan
1978, IORT pioneered in the U.S.A.:
- Howard University/N.C.I., Washington, D.C.
- Massachusetts General Hospital

44. Why IORT?
Partial breast Irradiation experience promising excellent local control and acceptability by patients
Single fraction
Treatment delivered in sterile environment, reducing risk for infection
AIMING RADIATION where RADIATION IS NEEDED

45. Intraoperative Radiation Devices
Beam
Delivery time
Sites
Applicators
IntraBeam
photon 40/50 kV
20 min
Breast, skin,
gyn, brain
cm Reusable
Axxent eBx
photon 50kV
Breast, skin, gyn
1 - 5-cm Single use
Mobetron
electron 4-12MeV
2 min
Breast, skin, gyn, rectal, pancreas, sarcoma, pediatric
cm Reusable
Ash, RB, et al, Oncology, 107 (2013)

46. IORT Systems of kV versus MV Devices
Carl Zeiss INTRABEAM and Xoft Axxent eBx vs IntraOp Medical Mobetron

47. Carl Zeiss IORT IntraBeam System
Arm stand with x-ray source
X-ray source
Control Workstation

48. Solid applicator and balloon
Applicator on the x-ray source
Solid applicator size available:
1.5, 2.0, 2.5, 3.0, 3.5, 4.0,
4.5, 5.0 cm in diameter, labeled by
A, B, C, D, E, F, G, and H for the part number. Reusable 100 times.
Balloon size available: 3.0, 3.5, 4.0, 4.5, 5.0 cm in diameter. Single use.

49. Spatial distribution of X-ray beam
50 kV, 40 µA
-1.5 mm
+1.5 mm
Gy/min

50. IORT Procedure with Solid Applicator
Step 1: The lumpectomy, immediately following tumor removal.
Step 2: After the surgeon has removed the tumor, the radiation oncologist positions the INTRABEAM applicator in the area of the breast where the tumor was located.
Step 3: Low energy radiation is delivered locally to the targeted tissue in the tumor bed, minimizing healthy tissue exposure to radiation.
Step 4: After minutes of radiotherapy, the applicator is removed and the surgeon then closes the incision.

51. Carl Zeiss IORT IntraBeam System in OR
Radiation from a mini-x-ray source of 50kV
Drape
Applicator
Lead Shield
A solid applicator with X-ray source ready to insert

52. Why the excitement for IORT?
TARGETED INTRAOPERATIVE RADIOTHERAPY
vs.
WHOLE BREAST RADIOTHERAPY
TARGIT-A TRIAL
Lancet Vol. 376
July 10, 2010

53. PATIENT SELECTION for TARGIT
Age: 45 or older suitable for wide local excision
Unifocal invasive ductal carcinoma (lobular was excluded)
Tumor size < 3.5 cm
Clinically N0
ECOG performance 0-3
No neoadjuvant chemotherapy

54. TREATMENT PARAMETERS Lumpectomy and Sentinel Lymph Node (SLN) Biopsy
If negative SLN, sizing of the lumpectomy cavity and placement of IORT device
Ultrasound for measuring skin-to-device distance
Placement of shield to protect heart and lung
Dosimetry in preparation for treatment delivery
Single dose of 20 Gray prescribed to the surface of the applicator

55. TARGIT-A Trial with IORT
• Four year median follow-up
• Local recurrence
•0.95% WBI with EBRT
•1.2% IORT with IntraBeam
Vaidya et al in 2010
3,451 patients as of 2013
• Local recurrence compared with ELIOT trial
• 3 year median follow-up
• 2.3 % IORT with electrons

56. IORT FOR BREAST CANCER: MERCY MEDICAL CENTER
September 7, February 20, 2014,
67 patients
68 IORT delivered
(1 pt with bilateral breast cancer)

57. 12 patients received additional whole breast irradiation:
beginning of IORT program
Margins
multifocality
2 patients had mastectomy
(multiple involved margins)

58. COMPLICATIONS Intraoperative: None Post-operative:
erythema infection dehiscence
COSMESIS: good to excellence

59. CONCLUSIONS
Large body of publications supporting that PBI in selected group of patients can optimize local control while minimizing radiation toxicity.
TARGIT-A trial showed comparable results to PBI.
Further trials are in progress using IORT (TARGIT-US) as a registry trial following breast conserving surgery.

60. Thank You! Muchas gracias!!