1. The ART of sparing HEART
Dr. Tabassum Wadasadawala
Assistant Professor, Radiation Oncology, TMC, ACTREC

2. Cardiac sparing techniques
Use of appropriate technique
3DCRT
IMRT/IGRT
Protons
Increasing distance between heart and chest wall
Respiratory gating
Prone position
Cardiac gating
Reducing Target volume
Accelerated Partial Breast Irradiation (APBI)
Avoiding boost in select cases

3. Simple means: 3DCRT on LA/Co
Benefits majority of patients
3DCRT plans employing simple heart blocks must be practiced if PTV coverage not compromised

4. IMRT/IGRT Dosimetric advantage Various techniques
RNI and in patients with significant heart volume within RT fields
Various techniques
Selection of appropriate technique depending up on the target volume
Combining with other techniques
Further reduction in cardiac dose in conjunction with prone or breath hold
Image guided radiotherapy
Potential for OAR sparing, dose escalation and adaptive RT
Extensively investigated
Post BCT and MRM with/without RNI and SIB
Impact on acute and late skin toxicity known
Lack of long term cardiac safety and second cancer data
Compared to 3D-CRT, IMRT may significantly reduce radiation dose to the myocardium in patients with left-sided breast cancer when the internal mammary nodes were included in the radiation fields because of the steep dose fall off away from the target volume. (Popescau IJROBP 2009, Landau D)
The superiority of IMRT over 3D-CRT for left-sided breast cancer was particularly beneficial in patients with a significant heart volume (more than 1 cm) included in the radiation fields.
caution should be used in comparing studies, as many studies included low numbers of patients, and extent of breast and nodal tissue covered differs from one study to another

5. Randomized trial of Helical Tomo vs Tangents
TomoBreast trial (N=123, results reported on 69)
Control Arm: 50Gy/25#+16Gy/8# sequential boost
Experimental Arm: 42Gy/15# with SIB 51Gy/15# with HT
Primary endpoint: reduction of cardiac & pulmonary toxicity
2 year toxicity grade ≥1
2D RT (N=32)
HT (N=37)
p value
Skin
60%
30%
0.056
Heart (LVEF)
4.8%
4.6%
0.744
Lung (FEV1)
20.8%
14.8%
0.422
Lung (DLCO)
29.2%
7.4%
0.047
Minimum FU of one year
Quality of life also better in HT arm
Van Parijs et al Radiat Oncol :80
Versmessen et al. BMC Cancer 2012

6. Tomotherapy for bilateral breast cancer
Breast/Chest wall with Boost (at least on one side)
Tangents
FIF-IMRT HT
TD-3DCRT
TD-IMRT
Total lung
MLD
V40
V30
V20
V10 V5
9.76 (1.26)
7.73 (1.22)
9.53 (1.22)
12.36 (2.06)
24.60 (5.80)
44.15 (7.97)
9.34 (1.34)
8.94 (2.19)
10.98 (2.56)
13.32 (2.89)
22.25 (4.47)
38.48 (6.74)
7.24 (0.91)
1.59 (0.88)
4.37 (1.29)
8.38 (1.70)
18.02 (3.51)
36.00 (5.03)
8.07 (0.56)
6.43 (1.26)
8.07 (1.31)
10.05 (1.30)
15.97 (1.58)
7.36 (0.96)
5.17 (2.12)
6.80 (2.26)
8.67 (2.29)
14.40 (2.19)
33.91 (4.13)
Heart
Mean
6.07 (1.87)
30.51 (6.35)
4.83 (3.17)
14.25 (8.78)
4.56 (1.07)
20.33 (6.57)
5.06 (2.39)
16.76 (7.17)
4.70 (2.67)
12.82 (6.66)
HT is both pulmonary and cardiac sparing for bilateral irradiation of breast/chest wall with SIB: need to validate the results in homogenous cohort
T Wadasadawala, Accepted in BJR

7. Proton therapy Definite radiobiological and dosimetric advantage
Drawbacks:
Limited clinical experience
High cost
Set up uncertainties
Lack of skin sparing
Respiratory motion
Feasibility of treating all beams daily

8. Respiratory gated radiotherapy
HEART
LAD FB
DIBH
Moderately deep breath hold is the key to achieving greatest cardiac sparing
Koremann et al RO 2005

9. Techniques of breath hold monitoring
CINE MODE
VARIAN RPM
ABC DEVICE
AlignRT
CBCT
EPID

10. Respiratory gated radiotherapy
Treatment parameter
Value
No of BH per field
2.5
Median duration of BH
22 s (10-26)
Median treatment time
18.2 min (13-32)
Improvement in cardiac dose
90%
Unable to do BH
1-14%
Inability to maintain an airtight seal with the mouthpiece
(dental problems or dentures)
Inability to maintain BH for adequate time (>20sec)
Psychological reasons
Inability to understand the procedure

11. Randomized cross over study
N=23 (19 BCT & 4 MRM)
Randomized cross over study
V-DIBH for fractions 1-7 & ABC for 8-14 with daily EPIDs
CBCT on 1,4,7,8,11,14
Similar OAR sparing & set up errors with both (≤ 5mm)
Error
V-DIBH (N=23)
ABC (N=23)
P value
Set up time
9 min
11 mins
0.04
Planning CT time
24 min
27 min
0.02
Patient comfort score
Higher for V-DIBH
0.007
Radiographer satisfaction score
0.03
Heart volumes were significantly smaller with v_DIBH, suggesting a different physiological response between a machine-initiated breath-hold (ABC_DIBH) and a voluntarily-initiated breath-hold (v_DIBH).
Barlett FR RO 2013

12. Supine 3D-DIBH vs. Supine Free breathing-IMRT
3D-DIBH better for LAD & heart sparing
Other advantages compared to IMRT:
Reduction in MUs
Reduction in integral dose and risk of second cancers
Reduction in dose to C/L lung and breast
Simpler planning
Possibly less impact of positioning errors
Increased clinical and financial efficiency (220%)
LAD (1.76 vs 2.47 Gy) & heart (0.85 vs. 1.55Gy) with 3D-DIBH
Supine DIBH + VMAT: Beneficial if Dmean heart with 3D-DIBH plan > 3.2 Gy but at the cost of increased dose to the C/L lung and breast
(Osman RO 2014)
Reardon KA, Med Dosi 2013
Osman RO 2014

13. Supine 3D-DIBH vs. Supine IMRT-DIBH
IMRT results further reduction of dose in the heart and LAD-region in breath-hold
Dosimetric study in 20 patients
Mast ME RO 2013

14. Benefit of DIBH proven on Cardiac gating
CT planning in free breathing and DIBH
Treatment delivery using ABC device
Cardiac MRI done after completion of RT
ECG gated axial MRI images acquired in late diastole (LD), mid diastole (MD) & systole
Image fusion done using chest wall, aorta, intervertebral disc & spinal cord
MRI-LD
MRI-MD
MRI-S
Heart volume FB
DIBH
Difference
628
513
115
539
461 78
529
446 83
LV Volume
Relative reduction
16.4
3.1
85%
15.5
1.9
92%
15.9
1.6
95%
Strong correlation between noted between MRI-defined whole heart and LV V22.5Gy reduction via ABC
Krauss DJ IJROBP 2005

15. Prone positioning Breast (pendulous) falls away from the chest wall
Reduction in cardiac dose
Inconsistent data (63-87% patients benefit from prone technique)
Benefits only in large pendulous breasts
Target volume:
Not safe for chest wall treatment or deep seated TB
Reproducibility: major concern
CBCT is the solution but scanning increases cardiac dose and treatment time
Regional Nodal Irradiation: dosimetry, feasibility and reproducibility
Several studies have shown reduced coverage with prone technique

16. Randomized studies Mulliez et al (R+L) Kirby et al (R+L) Whole breast
Partial Breast
Supine (50)
Prone (50)
Supine (65)
Prone (65)
Dose
40Gy/15#
50Gy/25#
Technique
6 beam IMRT non opposing
2 beam IMRT
Simple with MLC for cardiac shielding
Breast size
Cup size C, mean vol 1000cc
Median cup C, 2/3 >500 cc
Reduction in dose NR
63%
23%
Increase in dose
27%
No effect in dose
10%
14%
Subgroup benefitted
WB-CTV >1000 cc for LAD mean only
WB-CTV >1000 cc for heart mean and LAD mean & max
Primary endpoint: acute moist desquamation.
improved dose coverage (p < 0.001); better homogeneity (p < 0.001); less volumes of over-dosage (p = 0.001); reduced acute skin desquamation (p < 0.001); a 3- fold decrease of moist desquamation p = 0.04 (chi-square), p = 0.07 (Fisher’s exact test)); lower incidence
of dermatitis (p < 0.001), edema (p = 0.005), pruritus (p = 0.06) and pain (p = 0.06); 2- to 4-fold reduction of grades 2–3 toxicity; lower ipsilateral lung (p < 0.001) and mean LAD (p = 0.007) dose; lower, though statistically non-significant heart and maximum LAD.

17. Variables affecting prone RT outcome
Difference in contouring: whole breast CTV delineation, safety margin for LAD
Technique of RT employed (3DCRT/IMRT)
Median breast size
Tumor bed location and delivery of SIB
Parameters reported heart/LAD/both: volumetric (V25Gy) or dosimetric (Mean dose)
What is more important: Heart or LAD
Those who gain through heart protection are not always those who benefit through LAD exposure (19-33% discordance)
LAD important: Significant consequences, closest to radiation beam, displacement of the heart in prone position is greatest supero-laterally
Prone IMRT could be considered in all patients

18. Propositions for case selection
Mulliez & Kirby et al:
Right-sided tumors
Left-sided tumors and large breasts
Left-sided tumors and small breasts in whom comparative planning shows an advantage for prone position
Chen et al:
Breast depth in prone breast < or > 7cm
Breast depth Δ (prone – supine) < or > 3cm
Breast width Δ (supine – prone) < or > 4cm
Varga et al: Statistical model comprising of
BMI
Distance between LAD and CW
Area of heart included in the radiation field on a single CT scan at the middle of the heart in supine position
Zhao et al: weighted SVM (Support vector machine)
Chen J Rad Res 2013
Varga Acta Onco 2014

19. Position
No started on planned position
No completing all #
No requiring change of plan
Supine
25 (100%)
192 (100%)
2 (8%)
Prone
21 (84%), Out of tolerance set up errors
173 (90%)
8 (24%)
Position
Systematic error (mm)
Random error (mm)
Reduction in CW/clip motion (mm)
CTV_PTV expansion (mm)
Supine
2.7 ± 0.5 10
Prone
0.5 ± 0.2
12-16
Causes of greater set up error: shoulder discomfort or pain, underarm discomfort, suboptimal tattoo placement (skin folds, away from midline), epigastric circumference >40cm and seroma >25cc

20. Higher for V-DIBH for the first fraction
Measure
Supine V-DIBH (n=28)
Prone (N=28)
P value
CBCT Data (clip based match) ∑ σ
≤3.0 mm
≤ 6.5 mm
<0.05
≤ 3.5 mm
≤ 5.4 mm
OAR doses
Heart mean
LAD mean
0.4 Gy
2.9 Gy
0.7 Gy
7.8 Gy
<0.001
Treatment set up
5 min
3 mins
0.01
Beam on time
24 min
27 min
0.004
Patient comfort score
Higher for V-DIBH
<0.01
Radiographer satisfaction score
Higher for V-DIBH for the first fraction
0.06
Randomized 34 but evaluable 28 (>750 cc) Median breast volume
Supine VBH provided superior cardiac sparing and reproducibility than a free-breathing prone position for large breasted women Bartlett RO 2015

21. Prone + IMRT Prone IMRT superior to any supine treatment only for
Heart
I/L Lung
Prone IMRT superior to any supine treatment only for
Right-sided breast cancer patients for lung sparing
Left-sided breast cancer patients with larger breasts (≥ 600 cc)
The influence of treatment techniques in prone position is less pronounced for cardiac sparing
May be beneficial for SIB delivery
Prone better by obtaining better conformity indices, target dose distribution and sparing of the organs-at-risk.
N=18 unselected patients
Mulliez et al, Rad Onc 2013
Brenner et al JAMA 2013

22. Prone for Regional nodal irradiation
Traditional 3DCRT plans provide inadequate nodal coverage
Prone compared to supine, and IMRT compared to 3DCRT, lowered heart and I/L Lung doses with adequate coverage
Low dose to C/L lung, breast
Significant spinal cord dose
Match line problems
Reproducibility issues
Inverse plan IMRT, complex treatment planning
Patients with higher BMI were more likely to have redundant breast tissue suspended in the same axial plane as the nodal targets in the prone position, necessitating obliquity of the SCV field using a 90 degree couch rotation and gantry rotation of the SCV field matched by a collimator rotation of the tangent fields. These manipulations resulted in a subtle decrease in target coverage versus the supine position. If used in actual treatment delivery, they would greatly increase treatment complexity, and eliminate the ability to gantry rotate the SCV field off the spinal cord and esophagus. If treatment were delivered through the device a significant skin reaction would undoubtedly occur. Second, relatively less attention is given to arm position on a day to day basis when treating prone tangents alone. In the setting of 3-field treatment, arm position would assume much greater importance. The position of the arm has the ability to greatly affect the depth of the SCV lymph nodes by introducing or removing redundant tissue versus the day of simulation. Also, introduced skin folds could serve as a nidus for skin reaction. To circumvent these difficulties, a prone board modified for 3-field treatment would need to allow removal of the segment of board overlying the ipsilateral
SCV, while maintaining adequate support for the ipsilateral shoulder, and with proper bracing to ensure day to day identical positioning
of the ipsilateral arm. Construction of the board with modular pieces, with the ability to remove components as necessary, could
make such a device a reality.
Sethi R RO 2012

23. SUMMARY Selection of technique based on the target volume Breast Alone
Breast + SCF ± Ax: Supine DIBH irrespective of breast size
All breast size
Supine DIBH
Large breast size
Prone without DIBH
Small breast size
Supine/Prone
depending up on
Various propositions
Good compliance
to breath hold
Poor compliance