New techniques in breast radiotherapy
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Transcript of New techniques in breast radiotherapy
NEW TECHNIQUES IN BREAST RADIOTHERAPY
XENOPHON VAKALISRADIATION ONCOLOGIST
MEDICAL CENTER OF ATHENS&
401 MILITARY HOSPITAL OF ATHENS
HELLENIC SCHOOL OF MASTOLOGY: 17-18 SEPTEMBER 2010, ATHENS
Historical Perspective
Interstitial Radium Brachytherapy for Breast Cancer, 1917
Radiotherapy for Breast Cancer, London Hospital, c. 1917
Prospective Randomized Trials of Lumpectomy +/- Radiotherapy
Trial Pt # TumorSize-cm
Surgery % Failure - RT
% Failure + RT
NSABP 1265 <4.0 WE 36 12
Milan 601 <2.5 Q 24 6
Radiation Therapy for Early Stage Breast Cancer Following Lumpectomy
Rationale: Addition of whole breast irradiation following lumpectomy yields local control rates comparable to mastectomy
Treatment: Whole breast irradiation 45-50 Gy to the entire breast 60 Gy to the lumpectomy cavity + margin1.8 – 2 Gy fraction given 5 days/ week5 – 7 week total treatment duration
Whole Breast Irradiation
External Beam
Treats “whole breast”
Large volume of incidental tissues
Requires protracted (6—7 week) delivery
Breast Irradiation Technique
1,234 patients - T1 – T2, N 0 (80% T1)- ER positive - 71% - Median F/U: 69 months
Accelerated Whole Breast Irradiation:Reducing the burden of careCanadian Phase III Randomized Trial:
42.5 Gy – 16 fractions – 22 days vs.50 Gy – 25 fractions – 35 days
In-Breast Recurrence
(%)
Excellent/ good
Cosmesis (%)
Accelerated WBI
2.8 76.8
Standard WBI 3.2 77.4
Accelerated Whole Breast Irradiation:A Phase II clinical trial of a 4 week course of RT for breast cancer using hypo fractionated IMRT with a concomitant boost.
4 week course – 20 treatments– 45 Gy whole breast dose– 56 Gy boost dose
Results:– 16 patients treated– Acute toxicity: Grade I 57%, Grade
II 43%
Cuzick et al: Recent Results Cancer Research 111:108-129, 1988
Overall survival: radical mastectomy + / - RT
First 10 years Next 25 years
Overall Survival
XRT better XRT worse
XRT better XRT worse
XRT better XRT worse
Cardiac MortalityBreast Ca Mortality
Cuzick JCO 12:452, 1994
The shape of the breast and the position of the heart in relation to the chest wall can vary enormously
Decrease cardiac Exposure to RT
Partial Breast Irradiation Decubitus or Prone positions Breath Hold Technique Respiratory gating technique Proton therapy
Radiation techniques
Remouchamps et al 2003 Lu et al et al 2000
Breath hold in deep inspiration
Active Breathing Control + IMRT
Cardiac Sparing
Heart V5 V10 V20
Proton 4.1 2.7 1.5
Photon/Electron
33.2 20.8 10.4
PWTF 19.7 12.0 9.5
V5 Volume receiving 5% of the dose
Late cardiac morbidity (EBCTCG,Lancet 2000;355:1757-1770)
Breast cancer mortality reduced by 13%
Increase in annual mortality rate from other causes by 21%
Increase primarily due to excess deaths from cardiovascular causes
Cardiac effects may not emerge until 15 yrs after treatment
field
Maximum Heart Distance (MHD)
Heartcontour
Breastcontour
Figure 1a. Customized prone breast board with adjustable aperture and wedge for contralateral breast.Figure 1b. Ipsilateral breast and anterior chest wall hang in a dependent fashion away from the thorax while the ipsilateral arm is placed above the head
Goodman
Figure 6. Left breast irradiation using prone breast IMRT technique can spare left ventricle and coronary arteries.
Goodman
Transaxial
Sagittal
3-DCRT for left prone breast radiation:
Improved targeting and avoidance of lung
60 Gy
50 Gy
45 Gy
Lumpectomy
PTV
Elsewhere Failure (Outside Lumpectomy Region)
No XRT XRT Randomized Trials (BCT)
# Cases
Follow-up Interval (mos)
Crude % Crude % Ontario
837 43 15/421 3.5 4/416 0.9
Milan III
579 109 8/280 2.8 2/299 0.6
NSABP B06
1265 144 17/636 2.7 24/629 3.8
Uppsala-Orebro
381 33 3/194 1.5 1/187 0.5
Finland 152 80 4/72 5.5 4/80 5.0
The majority of cancer recurrences in the treated breast occur at the
lumpectomy site
Pattern of In-Breast Cancer Recurrences Following Breast
Conserving Therapy
Potential Benefits of Partial Breast Irradiation
Reduce time and inconvenience of BCT Improve documented underutilization of
breast conserving therapy (BCT)? Potentially reduce acute and chronic
toxicity Reduce burden of care for patients Eliminate scheduling problems with
systemic chemotherapy
Rationale for Partial Breast Irradiation (PBI)
10%-40% of those who are candidates for breast conservation therapy actually do not receive it.
Why?– Patient’s choice– Complex and prolonged treatment course
can be inconvenient for those with poor access to a radiation facility, the elderly and working women
– Physician bias
Techniques for PBI
Interstitial brachytherapy with HDR or LDR
Intracavitary brachytherapy with Mammosite
Intraoperative electron beam therapy
3D conformal radiation therapy Proton beam
Partial breast irradiation techniques
InterstitialBrachyther.
IntracavitaryBrachyther
Intraop.RT
3DConformal RT
Dose 34 Gy in 10 frIn 5 days
34Gy in 10 frIn 5 days
20-21Gy in single fraction
30 Gy in 5 fr. In 10 days
Target 1.5 cm margin around WLEcavity
1cm aroundWLE cavity
Visual by surgeon and radonc perop
2.5cm margin around WLEcavity
Pros Many dwell positions forIrreg. cavity
Ease of placement andplanning
Single doseSpares skin
Fits with standard RTmachines
Cons Operatordependent
High costFewer dwellpositions
RT before path knownSpecialised centres only
Larger fields(respiration) and more normal tissue
Accelerated Partial Breast Irradiation
Treatments delivered twice daily (with treatments separated by six hours) for 10 treatments delivered in 5 treatment days.
Delivery of radiation limited to lumpectomy site with a margin of normal tissue.
Each treatment takes approximately 10 minutes to deliver.
Accelerated Partial Breast Irradiation
Benefits:– Limited radiation exposure to normal
tissue– Treatments completed in one week
instead of six weeks
Accelerated Partial Breast Irradiation
Limitations:– May require additional surgical
procedure – Requires twice daily treatment– Newer modality with far fewer
patients treated and much shorter follow-up
– As of now, no direct comparison with standard radiation
Who is eligible for PBI?(Off study)
Tumors < 3 cm Negative margins (> 2mm) Node negative Invasive ductal carcinoma or DCIS Older women (>45 yrs)
Revised Consensus Statement for Accelerated Partial Breast Irradiation, 12/8/05
Interstitial brachytherapy
Catheters are placed intraoperatively or later; usually 2 planes
Typical doses with HDR = 30-36 Gy and LDR = 45-60 Gy
Treatment delivered over one week.
Patient Selection for Breast Brachytherapy
Patients older than 45 Tumors less than 2 cm. in size >2mm. Margins Preferably Infiltrating Ductal or loclized
low grade DCIS. No Lobular CA There must be at least 7mm. of tissue
between the catheter surface and the skin of the breast.
Advantages of Breast Brachytherapy vs. External Beam RT
6 weeks (30 fractions) Homogeneous dose Logistical problem for
patients Difficult for frail, elderly,
or chronically ill patients Interferes with schedule
of working women Some BCT candidates will
opt for mastectomy
5 days (10 fractions) Dose is higher to tissue
at greatest risk for sub-clinical malignant cells
Reduction in skin, cardiac and lung dose
Ideal for patients who live far from RT Center
Convenient May increase number
of women treated with BCT
Disadvantages of Breast Brachytherapy vs. External Beam RT
Noninvasive Can cover nodal regions Treats multi-centric
carcinoma Low complication rate Linear accelerators
widely available Most radiation
oncologists experienced
Invasive Not useful for treatment
of nodal basins May miss tumor foci in
other quadrants Low, but definite risk of
infection and/or fat necrosis
Requires special skills for performing; in placing catheters and dosimetry
MultiCatheter PBI: HDR/ LDR
Institution
Pt. No.
Median age
F/U mo.
T size (cm)
median
N+%
ER +%
Tam%
LR%
Exc/ good
Cosmesis%
Oschner 51 63 75 1.4 18 - - 2 -
Beaumont 199 65 65 1.1 12 - 57 1.2 99
Tufts-NEMC 32 63 33 1.3 9 79 61 3 88
VCU 44 62 42 1.2 18 - 66 0 80
Nat. Inst. Onc.
Budapest45 56 81 1.2 2 82 16 6.7 97
Guys Cs 137 49 58 75 2.5 46 - - 18 81
61 mo. 5% 89%61 y 1.4 cm17.5%Average:
Breast Brachytherapy
There has got to be a better way than all of those needles.
Mammosite device from Proxima Therapeutics may be the answer.
FDA approved the device in May 2002
Mammosite® Breast Brachytherapy Applicator
• Simplified brachytherapy method for PBI
• Dual lumen single catheter with expandable balloon at
end• Balloon expands to fill the
lumpectomy cavity• Radiation dose prescribed
to 1 cm beyond balloon surface
• Uses 192Ir (HDR) as the source
• FDA approval May 2002
MammoSite PBI
5th Int. Meeting ISIORT Madrid, June 2008
Volume Definition
PTV: GTV + 1.5 – 2.0 (clinical margin) + 0.5 (setup margin)
excluding skin and chest wall
Skin: 5 mm depth below skin surface
GTVPTVSkin
Difficulties with Mammosite
Balloon must conform to cavity shape without air gaps. Device explanted in ~ 10-15% of pts.
Ideal is to have 7 mm b/w balloon and skin to decrease risk of erythema.
Very dependent on surgical placement.
CT Planning for Mammosite Brachytherapy
Isodose Lines
50%
80%
100%
120%
140%
200%
Mammosite® balloon
3-Dimensional rendering of applicator surface and prescription dose cloud.
Prescription Dose
34 Gy 10 fractions
over 5 -7days
MammoSite PBI
Institution Pt. No.
Median age
F/U mo.
T size (cm)
median
N+%
ER +%
Local relapse
%
Exc/ good
Cosmesis%
Initial Multi- Institutional 43 69 48 1.0 0 - 0 80
Rush Univ. 112 64 -88%
Tis-T-17 - 0 80
Tufts-NEMC/ VCU 28 62 19 1.1 0 100 0 86
St. Vincent Hospital 32 62 11 97% T-1 9 94 - 86
Average: 64 y 26 mo 1 cm 4% 0% 83%
Toxicities of Mammosite
Seroma formation: Risk is increased with open technique for placement. In Beaumont series, found 60% risk with open cavity vs. 30% in closed cavity; overall rate of 45%, with 10% symptomatic.
Fat necrosis: Risk may be slightly lower than with HDR and no difference with placement technique.
Conclusion
The MammoSite RTS is the most commonly used PBI technique
MammoSite is minimally invasive, offers acceptable cosmetic results, and induces mild side effects
The duration of treatment is only five days making it more convenient for patients
The MammoSite RTS has criteria which prevent some patients from eligibility– New devices such as SAVI, ClearPath, and
Contura are overcoming those limitations
3-DCRT PBI
Institution
Pt. No.
Median age
F/U mo.
T size (cm)
median
N+%
ER +%
Local relapse
%
Beaumont 92 62 23 - 2 - 0
NYU 78 67.5 28 0.9 0 100 0
MGH 61 6212
(min) 0.9 0 - 0
RTOG 0319
42 61 - 0.85 - - -
Summary: 273 63 21 0.9 < 1 0
Accelerated Partial Breast Irradiation:Summary
Accelerated partial breast irradiation allows patients to complete a course of treatment in one week as opposed to the standard six weeks.
Treatment limited to part of the breast may be associated with less morbidity of treatment and better cosmetic outcome.
Hopefully, the randomized, prospective NSABP trial will answer the question of equivalence of partial and standard breast irradiation.
NSABP B-39/RTOG 0413 TrialPhase III
Stage 0, I-II breast cancer treated by lumpectomy
Randomization
WBI• 50-50.4 Gy (1.8-2.0 Gy)
Fractions to the whole breast followed by boost to 60 -66.6 Gy
PBI• 34 Gy in 3.4 Gy fxs bid
Mammosite® or Multicatheter brachytherapy
OR• 38.5 Gy in 3.85 Gy fxs bid
3D-CRT
Endpoints
Primary: in-breast tumor recurrence
Secondary:– Distant disease-free survival– Overall survival– QOL: Cosmesis, fatigue, symptoms,
burden of care
5th Int. Meeting ISIORT Madrid, June 2008
Zeiss Intrabeam®
-50 kV x-ray source at the end of a 15 cm long, 3.5 mm diameter tube.
-Spherical applicators with diameters of 15-50 mm in steps of 5 mm
-Dose rate of about 2 Gy/min at 1 cm in water
The pliable breast tissue is wrapped around the applicator. Subcutaneous stitches aid conformation, while ensuring that the skin is at least 1cm from the
applicator surface.
Intraoperative Radiation Therapy (IORT) for PBI
TARGIT trial is comparing whole breast irradiation to IORT delivering a single dose of 20 Gy. Primary accrual is in Europe.
Using the Intrabeam Photon Radiosurgery System, 50 kV x-rays.
Trial has enrolled 900 patients with target of 2200 patients.
Trials of partial breast RT
Trial Target accrual RT Technique Duration of RT
NSABP B-39 9000 Multisource Ir-192
5 days
TARGIT 3000 IntraoperativeXrays
1 day
ELIOT 2000 Intraoperativeelectrons
1 day
IMPORT Low 2000 External beamIMRT
3 weeks
GEC-ESTRO 1170 Multisource Ir-192HDR/PDR
2.5-4 days
Intensity Modulated Radiation Therapy (IMRT)
Dose distribution to breast with standard tangential fields
Dose distribution to breast using IMRT
Intensity Modulated Radiation Therapy (IMRT)
Phase III Randomized Study of Intensity Modulated Radiation Therapy Versus Standard Wedging Technique for Adjuvant Breast Radiotherapy
J. Pignol, et. al.Toronto, ON and Victoria, BCPresented ASTRO 2006, Plenary Session
Tangential Fields vs IMRT
358 patients randomized to standard breast irradiation or IMRT
Dose of up to 50 Gy + 16 Gy boost Endpoints of acute skin reaction and
incidence of moist desquamation
Tangential Fields vs IMRT
311 Patients included in analysis Decreased moist desquamation with
IMRT- 31% vs 48% (p=0.0019) Decreased moist desquamation in
inframammary fold with IMRT- 26% vs 43% (p=0.0012)
IMRT lowers the dose of radiation to the lung and to the heart (in patients with left sided breast cancers).
Intensity Modulated Radiation Therapy (IMRT)- Summary
We would not expect to see any differences in terms of recurrence or survival with IMRT
We would hope to see improvement in side effect profile
It may take years or decades to document a benefit in terms of cardiac toxicity
IMRT Conventional
Figure 4a. Transverse Dose Distributions
113 108 100 90 50Isodose in % 102 10
Goodman
Other Clinical Scenarios
Inoperable presentations Bulky, non-resectable recurrent cancer IMRT plans have sometimes looked
significantly better than 3D conformal, on a CASE BY CASE basis
5th Int. Meeting ISIORT Madrid, June 2008
Conclusions from Proton Therapy Study
- Protons spare non target breast tissue - reduction of 40%-45% vs. mixed modality
- Protons also spare contralateral lung & heart
- May permit retreat for pts with ipsilateral recurrence outside original field.
- Dose escalation?- Effect of neutrons in passively scattered
proton beams (Hall et. al.), but not in IMPT
5th Int. Meeting ISIORT Madrid, June 2008
DVH for non-target breast tissue
0
10
20
30
40
50
60
70
80
90
100
0 20 40 60 80 100
Dose(%)
Vol
ume(
%) Proton
IMRT
XRT
IMRT Protons Photons
El Ghamry et. Al. IJROBP 2002
5th Int. Meeting ISIORT Madrid, June 2008
Dose to Heart
Photons/Electrons Protons p-value Max dose (Gy) 3.2 0.8 0.001 Min dose (Gy) 0.2 0.01 .0001 D20 (Gy) 0.4 0.0 0.0001 D10 (Gy) 0.6 0.0 0.0001 D5 (Gy) 0.9 0.0 0.001
5th Int. Meeting ISIORT Madrid, June 2008
Dose to Lung
Photons/Electrons Protons p-value Max dose (Gy) 28 19 0.001 Min dose (Gy) 100 0.4 .001 D20 (Gy) 1.3 0.0 0.001 D10 (Gy) 2.5 0.4 0.0001 D5 (Gy) 4.1 2.1 0.005
5th Int. Meeting ISIORT Madrid, June 2008
Cost vs. Benefit: Protons vs. Photons
Benefit: Volume of non-target breast tissue receiving 50% of the prescribed dose is reduced 40% to 45%
Cost: WBI+B $10.6K3D-CPBI proton $13.2K
(+25%)3D-CPBI-photon $5.3K (-
50%) A. Taghian et. al. IJROBP. 65:1404-1410; 2006