The dosimetric impact of seroma volume changes over the ...wesleyzoller.weebly.com/uploads/1/3/3/9/13396224/__aamd_research_paper.pdfpatients in the treatment planning system for a

AAMD Journal Submission| Zoller , et al.

Cleveland Clinic | Medical Dosimetry Program Class of 2013 Abstract-Title

The dosimetric impact of seroma volume changes over the course of radiotherapy treatment on

sequential boost planning (Arm I) and a comparison of two concurrent hypofractionated boost methods

(Arm II) for breast cancer patients eligible for RTOG protocol 1005.

BY WESLEY ZOLLER B.S.RT(T) AND LISA ZICKEFOOSE B.A.RT(R)(T)(CV)

CO-AUTHORED BY ANDREW VASSIL , MD, ANTONIA FANNIN B.A.RT(R)(T), PING XIA , PHD, AND ERIC MURRAY, CMD

THE DEPARTMENT OF RADIATION ONCOLOGY

CLEVELAND CLINIC 9500 EUCLID AVENUE CLEVELAND, OHIO 44195

KEYWORDS

Seroma; Breast cancer; Radiation therapy; RTOG 1005

INTRODUCTION

Breast conserving surgery with adjuvant radiation

therapy is supported by mult iple clinical t rials as being a

safe alternative to total mastectomy.2 Outlined by Arm I

of RTOG Protocol 1005,1

one current standard of care for

external beam radiation (EBRT) is delivery of 50 Gray

(Gy) in 25 fract ions to the whole breast with a sequential

12 Gy photon or electron boost to the post-lumpectomy

bed delivered in 6 fractions. The addition of such a tumor

bed boost has shown to further decrease recurrence rates

for patients with invasive breast cancer.3

For early stage patients (stage I-II) undergoing

breast-conservation therapy, the goal of EBRT is to

deliver prescription dose to the target volumes while

minimizing excess dose to surrounding normal structures.

In terms of receiving boost dose in addition to the

tangential 50 Gy, normal breast tissue is of particular area

of interest and should be taken into account. By sparing

this normal breast tissue of irradiation beyond standard

whole breast doses, the potential exists to reduce site-

specific late effects, such as fibrosis.4,5

Excess dose may

also increase the risk of hyperpigmentation and other

acute side-effects.4,5

Despite being a reduced field, boost

Abstract: Purpose: 1. Evaluate the effect of seroma volume changes over treatment to assess indications for adaptive boost planning. 2. Dosimetrically compare concurrent IMRT photon and electron cavity boosts for breast cancer patients eligible for RTOG 1005. Methods: Eleven patients with clinically evident seroma volumes at the time of initial CT (CT1) who received a second CT (CT2) prior t o sequential

boost planning were chosen for this study. In Phase I, CT2 was fused onto CT1 for retrospective re -planning, with characteristics of both seroma volumes being recorded. As in RTOG 1005 Arm I, patients were planned to receive 50 Gray (Gy) in 25 fractions (fx) tangentially

with a 12 Gy/6 fx sequential electron boost to the cavity.1 Separate plans were optimized for each volume. For Phase II, patients were re-

planned using the CT1 volume receiving the RTOG 1005 Arm II dose of 40 Gy/15 fx with a concurrent 8 Gy/ 15 fx boost planned with both electron and IMRT tangential photons.1 Plans were evaluated based on dose to the heart, ipsilateral lung, and total ipsilateral breast

tissue (Breast PTV Eval). Results: For Phase I, seroma volumes decreased on CT2 by an average of 57.06% +/- 8.96%, p= 0.001. The V56 of the Breast PTV Eval decreased on CT2 boost plans by an average of 9.16% +/- 3.26%, p= 0.001. In Phase II, the V44.8 of the Breast PTV Eval was reduced for all electron boosts by an average of 16.24% +/- 8.08%, p= 0.001. Conclusions: For patients with clinically significant changes in seroma volumes, re-planning the sequential boost with a new CT may reduce excess dose to normal breast tissue, potentially

reducing late effects. For concurrent hypofractionated methods, electron boost technique had improved conformality compared to IMRT plans with reduced dose to normal breast tissue.


Cleveland Clinic | Medical Dosimetry Program Class of 2013 1 | P a g e

portals can result in a significant portion of the breast

receiving dose well beyond the tangential prescription.

A potential difficulty with generating a boost portal

from init ial simulat ion is the propensity for the post-

lumpectomy seroma to change in size over the treatment

course. The first objective of this study is to statistically

quantify the volumetric extent of this change to assess

consistency and significance. As a corollary, the second

objective is to determine the impact of this seroma

volume change on tumor bed dosimetry. With significant

decreases in tumor bed sizes, the possibility exists to

minimize boost portals by generating the boost plan from

a second computed tomography (CT) dataset acquired

near completion of the whole breast course. This

optimization may reduce excess irradiat ion to normal

breast tissue. Currently, RTOG 1005 requires that all

boost plans be rendered from the in itial CT simulation.1

This phase of the study will analyze tumor bed changes

during radiation therapy as well as assess any advantages

associated with acquiring a second CT prior to sequential

boost planning.

Hypofractionated courses for whole b reast radiation

have been studied with the primary advantage of reducing

total treatment time and associated cost. Arm II of the

RTOG 1005 study is testing a radiation schedule of 40 Gy

tangentially to the whole breast given in 15 fractions with

a concurrent or integrated boost of 8 Gy in these same 15

fractions. This boost may be given by electron, conformal

photon, or concomitant IMRT as preferred.1 Based on

this, the third and final objective of the study is to

dosimetrically compare two hypofractionated concurrent

boost methods for this course, electron versus tangential

IMRT photon. Analysis of tumor bed coverage and

critical structure avoidance may provide the means to

assess preferability between the methods .

METHODS AND MATERIALS

Phase I:

In this study, eleven previously treated early stage

breast cancer patients (stage I-II) with invasive carcinoma

of either b reast were retrospectively re-planned using the

standard fractionation schedule outlined in Arm I of

RTOG Protocol 1005. Patients with clinically evident

seroma volumes at the time of initial CT simulat ion (CT1)

were chose for this study sample. While each patient was

receiving the conventional 50 Gy in 25 fractions under

original radiat ion treatment, a secondary CT dataset

(CT2) was acquired around the fourth week of treatment

prior to boosting for the characterization of seroma

volume changes and to assess a need for adaptive boost

planning. All CT data was acquired using a Siemens™

SOMATOM®

CT-On-Rails Sensation Open system.

Contours of both Lumpectomy gross tumor volumes

(GTV) were delineated by a radiation oncologist in

accordance with RTOG Protocol 1005 guidelines using

MIM Software™ Version 5.4 (Cleveland, OH). All

contours and CT datasets were transferred to Philips™

Pinnacle3®

with AcQSim™ treatment planning system

version 9.0 for the purposes of retrospective re-planning

as seen in Fig. 1. The CT2 data and GTV contour were

then fused onto the CT1 data set using Philips™

Pinnacle3®

Syntegra™ fusion system with box-limited

cross-matching of mutual CT data of the affected breast

and chest wall. Using the treatment planning system, the

volumes of the two Lumpectomy GTV contours were

recorded for further analysis of volumetric changes over

the course of treatment. Along with these volumes , the

Lumpectomy clinical target volumes (CTV) ,

Lumpectomy p lanning target volumes (PTV),

Lumpectomy PTV Eval, and Breast PTV Eval were

delineated in this study for evaluation in accordance with

the RTOG 1005 planning guidelines and can be seen in

Fig. 2.1 Likewise, crit ical organs included the heart,

ipsilateral lung, contralateral lung, and total lung volume;

these structures were also generated within RTOG 1005

guidelines.1

The relation between initial GTV volume (cc)



and percent decrease, elapsed time between scans (days)

and percent decrease, delta volume (cc), and the percent

decrease were calculated. Pearson r regression and paired

t-tests were performed to determine correlation strength

and result significance.

To quantify the dosimetric impact of seroma volume

changes, tangential plans were rendered for each of the 11

patients in the treatment planning system for a Siemens™

Artiste®

linear accelerator with the capabilities to use both

6 and 10 megavolt potential as needed. Tangent fields

were designed to prescribe 50 Gy in 25 fractions to the

whole breast while meet ing dose and coverage constraints

outlined by Arm I of RTOG 1005.1 An example of these

fields can be seen in Fig. 3.1

Forward-p lanned control

point segmentation and/or

dynamic wedging were used as

necessary to meet these

constraints. With the fused CT2

contour and the CT1 contour

both present on the CT1 data set,

it was then possible to generate

composite sequential electron

boost plans optimized

individually for each volume

while maintaining identical

whole breast tangential fields.

The en-face electron boosts were

independently given uniform

expansions on each

Lumpectomy CTV (CT1 and

CT2) such that each

Lumpectomy PTV Eval received

the RTOG 1005 Arm I-specified 95% V58.9 associated

with each CTV.1

Electron boosts were planned at 100 cm

Source-to-Skin Distance (SSD) and the available electron

energies of 6, 9, 12, 15, 18, 21 megaelectron volts (MeV)

were selected to achieve optimal coverage based on the

protocol. Notable dose limiting volumes for p lan

acceptance specifically outlined in Arm I of the protocol

involved the volume of ipsilateral lung receiv ing 20 Gray

(V20), the mean dose to the heart (500 cGy Arm I), and

the V56 for the Breast PTV Eval.1

These objectives were,

therefore, the limits specifically analyzed

in this study for statistical dosimetric

comparison of the CT1 GTV and CT2

GTV p lans. In addition, the CT1 volume

sequential boost was evaluated in terms of

V58.9 coverage of the Lumpectomy PTV

Eval for CT2 to assess the possibility of

CT1 lumpectomy bed-optimized plans

under-treating the seroma site due to

changes throughout treatment.

Phase II:

In this phase, the same tangential

whole breast fields optimized for phase I

were re-prescribed to deliver 40 Gy in 15

fractions as in the hypofractionated

schedule of Arm II of RTOG 1005.1

Along

with this, the electron boost was re-

prescribed to deliver 8 Gy in 15 fract ions

concurrently to the CT1 volume such that

at least 95% of the Lumpectomy PTV Eval

received 45.6 Gy as mandated by Arm II.1

To provide a direct comparison, an 8 Gy in

15 fraction concurrent tangential IMRT

photon boost was generated compositely with the init ial

40 Gy tangent fields in a separate treatment plan. IMRT

fields were limited to the same gantry angles as the

tangent fields and were designed to be given



concomitantly as the fields were inverse-planned with

both prescriptions on for algorithmic evaluation. The total

maximum number of segments allowable for the two

beams was twelve, and each beam was required to have at

least three inverse-planned control points to qualify as

IMRT per RTOG 1005.1 The same Lumpectomy PTV

Eval coverage constraints were used as in the concurrent

electron boost, and some notable dose limiting volumes

for plan acceptance specifically outlined in Arm II o f the

protocol included the V16 for the ipsilateral lung, the mean

dose to the heart, and the V44.8 for the Breast PTV Eval.1

Analysis of these volumetric constraints was then used for

a dosimetric evaluation of a concurrent electron cavity

boost and a concurrent tangential IMRT photon boost by

comparison of coverage and critical structure avoidance

in identical manner to that of Phase I.

RES ULTS

Phase I:

Based on the volume readings of the physician-

contoured CT1 Lumpectomy GTV and the CT2

Lumpectomy GTV, the seroma volumes decreased in size

for each of the 11 patients with a mean reduction of

57.06% and standard deviation of 8.96% as shown in

Table 1. The min imum percentage decrease in volume

among the population sample was 46.12% with the

maximum reduction being 77.34%. The decrease in

seroma volume for the patients yielded a p-value of 0.001

and showed to be statistically significant over the course

of treatment. The average of the elapsed days between

CT1 and CT2 acquisition was 33.6 days +/- 5.14 days.

The minimum time separation between scans for the

population was 22 days with the maximum being 42 days.

The Pearson r correlation coefficient between the number

of elapsed days and the size decrease in percentage was

found to be 0.4869, p=0.1287. Thus, no correlation

between the two variables could be determined. For the

patient population, the size of the Lumpectomy GTV

contour on CT1 ranged from a minimum of 29.80 cubic

centimeters (cc) to a maximum of 116.85 cc. However,

no relationship between the size of the initial GTV

volume and the volume reduction percentage could be

determined as the Pearson r correlation value between the

variables was -0.0575, p =0.866. These results are shown

in Table 1.

The dosimetric impact of these volume changes was

assessed between the CT1 Lumpectomy GTV and CT2

Lumpectomy GTV sequential electron boost plans and the

results can be seen in Fig. 4. When compared to the CT1

retrospective boost plan, the CT2 plan showed to decrease

the V56 Breast PTV Eval for all cases. The V56 for this

structure was specifically outlined in Arm I of the RTOG

1005 Protocol as a dose constraint.1 On average, the V56

decreased by 9.16% +/ - 3.26% by re-planning with the

new volume, y ield ing a maximum decrease of 14.74%

and a minimum of 4.44%, p=0.001. This showed to be

statistically significant in terms of dose reduction to

normal breast tissue and results can be seen in Table 2.

For the entire population, the maximum change between

the boost plans for mean heart dose was 17.2 cGy, which

was less for the CT2-optimized boost. This was minimal

as all plans were well below the RTOG 1005 Arm I dose

constraint of 500 cGy mean dose to the heart.1 Likewise,

the maximum difference in V20 for the ipsilateral lung

between the plans was 0.55%, which was also less for the

CT2 Lumpectomy CTV optimized boost plan. All plans

accomplished greater than or equal to 95% coverage for

the V58.9 of the Lumpectomy PTV Eval, which was

specifically outlined as ideal in RTOG 1005.1

When

projected onto the CT2 volume, the CT1 volume-

optimized sequential boost plan still maintained this

coverage of the new contour for all cases, with the

minimum being 95.93%. Thus, this study did not show

evidence that failure to repeat CT simulation for boost

planning would lead to under-treatment of the seroma

volume.



Phase II:

Analysis of this phase showed a significant decrease

in the Breast PTV Eval V44.8 for all concurrent electron

boosts when compared to concurrent tangential IMRT

photon boosts. The average V44.8 decrease was 16.24%

+/- 8.08 for the electron plans, p=0.001—which indicates

better dose conformity with the electron boost plan and

can be seen in Fig. 5. The maximum decrease between the

methods was 28.07% with a minimum of 4.62%. Results

from this phase can be seen in Table 3. The Breast PTV

Eval V44.8 was a constraint specifically outlined for the

hypofractionated Arm II of RTOG 1005.1

For the mean

heart dose, the maximum variance was 53.5 cGy, which

was lower for the IMRT tangential photon boost.

However, all mean heart doses were well below the mean

dose constraint of 400 cGy outlined for the protocol.1

In

accordance, the V16 for the ipsilateral lung yielded a

maximum variance of 1.85% which was lower for the

concurrent electron boost. Both of these variances were

negligible in the planning process.

DISCUSS ION

Multip le studies have looked to assess the volume

changes of post-operative seromas throughout the course

of radiation treatment.6,7

The first objective of this study

was to evaluate the seroma volume changes during the

course for patients receiving the standard treatment

fractionation scheme (Arm I) outlined by RTOG protocol

1005.1

With this informat ion, it was then possible to

evaluate the dosimetric impact of these potential volume

changes as it pertains to cavity coverage and dose to

critical structures for the standard of care as described in

the protocol.1

The goal was to determine any indications

for acquiring a second CT data set prior to the planning of

a sequential boost.

The results from Phase I showed a statistically

significant decrease in the seroma volume during whole

breast treatment with an average decrease of 57.06% +/-

8.96% from CT1 to CT2. The average time between these

CT acquisitions was 33.6 elapsed days with a standard

deviation of 5.14 days. This time period is appropriate

and falls at approximately the fourth week of t reatment.

This, in turn, would maintain the time necessary for a

sequential boost to be planned on the new CT prior to

complet ion of the standard whole breast fractionation

course. The applicability of acquiring one additional CT

to accurately delineate such a large change provides the

benefit of reducing the treatment port volume by basing

the marg ins of the sequential boost field off of the new

reduced tumor bed volume from CT2. Analysis of the

individually optimized CT1 GTV versus CT2 GTV

sequential electron boost plans indicated that the volume

of normal breast tissue (Breast PTV Eval V56) treated was

decreased by an average of 9.16% +/- 3.26% while

variances on mean heart dose and lung dose were minimal

between the plans. This dose reduction to normal breast

tissue was found to be statistically significant, and could

play a role in decreasing associated acute and late effects

of radiation treatment.4,5

50 Gy in 25 fract ions

tangentially with a 12 Gy in 6 fract ion electron boost

mimics the conventional standard of care, and by

acquiring one additional CT dataset prior to boost

planning, it could be possible to eliminate treating

unnecessary normal tissue. By performing this adaptive

re-planning, treatment plans may have been able to more

easily satisfy the dose constraints, or even change a

structure dose from acceptable to ideal by trial

compliance criteria.

It was also necessary in this study to evaluate if the

plans optimized for the orig inal volume still p rovide

adequate coverage of the new GTV volume after the

change over the treatment course. For all eleven patients,

the original plan provided the necessary coverage of the

CT2 Lumpectomy PTV Eval set per RTOG 1005 Arm

I.1This indicated that although excess normal tissue may

have been treated, plans from the original volume would



not provide any potentially harmfu l under-dosing in this

study.

The second objective of this study was to compare

dosimetric outcomes for concurrent IMRT photon boosts

and concurrent electron cavity boosts given the

hypofractionated scheme (Arm II) for breast cancer

patients eligible for RTOG protocol 1005.1 In phase II,

the Breast PTV Eval V44.8 showed a significant decrease

for all electron boost plans when compared to IMRT

tangential photon boosts. The V44.8 reduced by 16.24 %

on average with a standard deviation of 8.08%. This

indicates a potential benefit to concurrent electron boost

planning as it reduced the dose to normal breast tissue

while provid ing a plan which was more conformal to the

target volume. Between the two methods, the dose

discrepancies were minimal in terms of mean heart and

ipsilateral lung dose.

CONCLUS ION

Tumor bed volumes may change significantly over

the course of treatment for early-stage breast cancer

patients receiving post-lumpectomy radiotherapy. Due to

the changes in the seroma volume, there may be benefits

in acquiring a second pre-boost CT dataset. Acquisition of

this new scan would allow not only an assessment of

seroma volume changes, but also an opportunity to

perform adaptive boost planning should the change render

it necessary. Ultimately, this could decrease the volume of

normal breast tissue receiving excess radiation,

potentially decreasing acute and late side effects

associated with this treatment site.4,5

The results from this

patient population indicate merit for secondary CT

acquisition for sequentially boosted breast cancer patients

and provide a recommendation for its usage. For

concurrent hypofractionated treatment methods, the

electron boosts were shown to be more conformal to the

target volume when compared with tangential IMRT

photon boost fields, and this resulted in a decrease in dose

to normal breast tissue. Again, this could potentially p lay

a role in reducing side effects of radiation treatment and

provide for better patient outcomes.

TABLES





REFERENCES

1. Vicini, F.; Freedman, G.; White, J.; et al. A

Phase III trial of accelerated whole breast

irradiation with hypofractionation plus

concurrent boost versus standard whole breast

irradiation plus sequential boost for early-stage

breast cancer. RTOG protocol 1005; 2012.

www.rtog.org

2. Morrow, M.; Strom, E.A.; Bassett, L.W.; et al.

Standard for breast conservation therapy in the

management of invasive breast carcinoma. Ca

Cancer J Clin. 5: 277-300; 2002.

3. Poortmans, P.M.; Collette, L.; Bartelink, H.; et

al. The addition of a boost dose on the primary

tumour bed after lumpectomy in breast

conserving treatment for breast cancer. A

summary of the results of EORTC 22881-10882

“boost versus no boost” trial. Cancer Radiother.

6-7: 565-570; 2008.

4. Collette, S.; Collette, L.; Budiharto, T.; et al.

Predictors of the risk of fibrosis at 10 years after

breast conserving therapy for early breast cancer;

a study based on the EORTC Trial 22881-10882

„boost versus no boost‟. Eur J Cancer. 17: 2587-

2599; 2008.

5. Mukesh, M.; Harris, E.; Jena, R.; Evans, P.;

Coles, C. Relationship between irradiated breast

volume and late normal t issue complications; a

systemic rev iew. Radiother Oncol. 104: 1-10;

2012.

6. Sharma, R.; Spierer, M.; Mutyala, S.; et al.

Change in seroma volume during whole-breast

radiation therapy. Int J Radiat Oncol Biol Phys.

75: 89-93; 2009.

7. Flannery, T.W.; Nichols, E.M.; Cheston, S.B; et

al. Repeat computed tomography simulation to

assess lumpectomy cavity volume during whole-

breast irradiation. Int J Radiat Oncol Biol Phys.

75: 751-760; 2009.

http://www.rtog.org/

Documents

The dosimetric impact of seroma volume changes over the ...wesleyzoller.weebly.com/uploads/1/3/3/9/13396224/__aamd_research_paper.pdfpatients in the treatment planning system for a