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

The ART of sparing HEART

Dr. Tabassum WadasadawalaAssistant Professor, Radiation

Oncology, TMC, ACTREC

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

Simple means: 3DCRT on LA/Co

• Benefits majority of patients• 3DCRT plans employing simple heart blocks must be

practiced if PTV coverage not compromised

IMRT/IGRT• Dosimetric advantage

– 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

Randomized trial of Helical Tomo vs Tangents

Van Parijs et al Radiat Oncol 2012 7:80Versmessen et al. BMC Cancer 2012

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

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

Quality of life also better in HT arm

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)

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

V5

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)

Tomotherapy for bilateral breast cancer

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

Proton therapy

• Definite radiobiological and dosimetric advantage

• Drawbacks:– Limited clinical

experience– High cost– Set up uncertainties– Lack of skin sparing– Respiratory motion

FB DIBH

Koremann et al RO 2005

HEART LAD

Moderately deep breath hold is the key to achieving greatest cardiac sparing

Respiratory gated radiotherapy

Techniques of breath hold monitoring

VARIAN RPM ABC DEVICE

EPID AlignRT CBCT

CINE MODE

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%

Respiratory gated radiotherapy

• 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

• 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 Higher for V-DIBH 0.03

Barlett FR RO 2013

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%) Reardon KA, Med Dosi 2013

Osman RO 2014

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

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 volumeFBDIBHDifference

628513115

53946178

52944683

LV VolumeFBDIBHRelative reduction

16.43.185%

15.51.992%

15.91.695%

Strong correlation between noted between MRI-defined whole heart and LV V22.5Gy reduction via ABC

Krauss DJ IJROBP 2005

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

Mulliez et al (R+L) Kirby et al (R+L) Whole breast

Kirby et al (R+L) Partial Breast

Supine (50) Prone (50) Supine (65) Prone (65) 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

NR 27% 63%

No effect in dose

NR 10% 14%

Subgroup benefitted

WB-CTV >1000 cc for LAD mean only

WB-CTV >1000 cc for heart mean and LAD mean & max

WB-CTV >1000 cc for heart mean and LAD mean & max

Randomized studies

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

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

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

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 1.3-1.9 2.6-3.2 2.7 ± 0.5 10

Prone 3.1-4.3 3.8-5.4 0.5 ± 0.2 12-16

Supine VBH provided superior cardiac sparing and reproducibility than a free-breathing prone position for large breasted women

Bartlett RO 2015

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 <0.05

OAR dosesHeart meanLAD mean

0.4 Gy2.9 Gy

0.7 Gy7.8 Gy

<0.001<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

Prone + IMRT

• 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

HeartI/L Lung

Mulliez et al, Rad Onc 2013Brenner et al JAMA 2013

• 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

Prone for Regional nodal irradiation

Sethi R RO 2012

SUMMARY• Selection of technique based on the target volume

• Breast Alone

• Breast + SCF ± Ax: Supine DIBH irrespective of breast size

Good compliance to breath hold

Poor complianceto breath hold

All breast sizeSupine DIBH

Large breast sizeProne without DIBH

Small breast sizeSupine/Prone depending up onVarious propositions