Five-field IMRT class solutions and dosimetric planning guidelines for implementing accelerated partial breast irradiation

    Five-field IMRT Class solutions and dosimetric planning guidelines for implementing accelerated partial breast irradiation Sarah Quirk, Petra Grendarova, Michael Roumeliotis PII: DOI: Reference:

S1879-8500(17)30266-7 doi: 10.1016/j.prro.2017.09.009 PRRO 822

To appear in:

Practical Radiation Oncology

Received date: Revised date: Accepted date:

29 March 2017 29 August 2017 20 September 2017

Please cite this article as: Quirk Sarah, Grendarova Petra, Roumeliotis Michael, Five-field IMRT Class solutions and dosimetric planning guidelines for implementing accelerated partial breast irradiation, Practical Radiation Oncology (2017), doi: 10.1016/j.prro.2017.09.009

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT Title: Five-field IMRT Class solutions and dosimetric planning guidelines for implementing accelerated partial breast irradiation

RI P

T

Short title: Class solutions and dosimetric planning guidelines for implementing APBI

Corresponding author: Sarah Quirk, PhD, University of Calgary

SC

403-521-3836

NU

[email protected]

MA

Authors: Petra Grendarova, MD, University of Calgary

CE

PT

ED

Michael Roumeliotis, PhD, University of Calgary

AC

Conflict of interest statement

The authors have no conflicts of interest.

ACCEPTED MANUSCRIPT Title: Five-field IMRT class solutions and dosimetric planning guidelines for implementing

RI P

Short title: Class solutions and dosimetric guidelines for APBI

T

accelerated partial breast irradiation

SC

Abstract

Purpose: A comprehensive set of planning guidelines was developed to aid in reproducible

NU

dosimetric results for external beam accelerated partial breast irradiation (APBI). Methodology for development of class solutions for dosimetric planning of the APBI technique, including dose

MA

constraint recommendations, is presented for target coverage and conformity as well as normal

ED

tissues.

Methods and Materials: A conservative patient setup was simulated on a TrueBeam™ linear

PT

accelerator and a comprehensive arrangement of gantry and couch angles were measured for

CE

clearance. This provided the foundation for available beam arrangements to develop reproducible and conformal five-field IMRT partial breast plans. Forty patients were planned. Patient plans

AC

were assessed according to anatomy specific features, such as laterality and seroma location within the breast.

Results and Discussion: Clearance tables are presented to give permissible gantry and couch orientations according to measurements facilitated by patient simulation. Beam arrangement class solutions are presented for left and right-sided APBI patients. Dosimetric recommendations are made based on the results of 40 patient plans. The median and range, describing target coverage and target conformity are reported, as well as normal tissue constraints for ipsilateral lung, ipsilateral breast, heart, liver, and contralateral breast. In all cases, the dose recommendations were at least as strict as multi-institutional accelerated partial breast irradiation

ACCEPTED MANUSCRIPT trials. In the case of ipsilateral lung and ipsilateral breast, the planning recommendations are more stringent.

RI P

T

Conclusions: Accelerated partial breast irradiation using a five-field IMRT technique was comprehensively developed and evaluated to provide recommendations yielding highly

SC

conformal and reproducible treatment plans. This provides a clear method to implement external

NU

beam APBI planning and delivery.

MA

Introduction

Breast cancer is the most common nondermatologic malignancy and is the second leading cause

ED

of cancer related death for women in Canada [1]. For patients diagnosed with early stage breast cancer, the current standard of care is breast conserving surgery followed by whole breast

PT

radiation therapy (WBRT), which is typically delivered in 16 to 25 daily fractions over 3 to 6

CE

weeks. For a subset of the early stage breast cancer patients, accelerated partial breast irradiation (APBI) is a treatment option aimed at reducing the volume of breast tissue that is treated and

AC

thus results in less toxicity. External beam APBI treatments have been investigated in large multi-institutional trials that have yielded equivalent survival short-term outcomes, but with mixed results relating to treatment related toxicities and cosmesis [2], [3], [4], [5], [6]. Based on these preliminary results, external beam APBI is likely to be more broadly implemented if the long-term results are favourable. In comparison to other partial breast techniques, such as brachytherapy or intraoperative RT, external beam expertise is widely available in radiation therapy departments and represents a reduction in resources compared to WBRT. External beam APBI has been administered and studied using a variety of radiation treatment techniques, including 3DCRT, IMRT, and VMAT [4], [7], [8], [9], [10]. In 2003, Baglan et al.

ACCEPTED MANUSCRIPT provided the outline for 3DCRT planning of APBI with recommendations for a three to five-field non-coplanar delivery technique [7]. The objective of that paper was not to provide rigorous

T

planning guidelines, but rather serve as a comprehensive APBI feasibility study. APBI planned

RI P

with IMRT has been established in literature to achieve better possible plan quality compared with 3DCRT [9]. Although VMAT has also shown highly conformal dose delivery in

SC

comparison to 3DCRT, it results in a significantly higher dose to the contralateral breast and lung

NU

[9], [10]. Because all current multi-institutional trials utilize 3DCRT or IMRT, coupled with these normal tissue concerns in the VMAT relevant literature, VMAT planning is beyond the

MA

scope of this work. This cohort of women has a long life expectancy, so their quality of life may be impacted by both cosmesis and the long term morbidities associated with increased dose to

ED

normal tissues.

PT

Large multi-institutional clinical trials have explored APBI but typically have not included

CE

recommendations for specific beam arrangements in their protocols or publications. Other literature has provided some guidelines for beam arrangements [7] without a comprehensive

AC

framework for implementing their recommended practice. This is largely because determining the available beam and couch angles that will avoid patient collisions are unknown and difficult to measure and tabulate. Knowledge of the available clearance is necessary to develop a reproducible planning strategy, otherwise centres adopting APBI would typically implement conservative planning strategies, resulting in plans that meet trial criteria but tend to be less conformal [11]. The available solution space for beam arrangements based on seroma location must be characterized. One barrier in optimizing the possible beam arrangements is a clinically usable way to determine gantry, couch, and patient clearance at the time of treatment planning. Vendor specific clearance

ACCEPTED MANUSCRIPT graphs exist [12], [13]; however, they do not account for clearance near patients or immobilization devices and are not in a format conducive to daily treatment planning use. The

T

factors that influence clearance for external beam APBI are patient characteristics including the

RI P

immobilization device, arm position, the patient’s anterior-posterior separation, and the seroma location (i.e. left- vs right-sided breast; lateral vs. medial within breast). The seroma location

SC

guides the assignment of the isocentre which, in turn, influences the couch position relative to

NU

the gantry.

MA

The purpose of the current study is two-fold. First, is to develop a highly reproducible and comprehensive sliding window IMRT beam arrangement planning strategy. The IMRT planning

ED

strategy used a simulation setup to assess the available gantry and couch angles that are dependent on seroma location and to a lesser degree patient body habitus and arm/elbow

PT

position. Second, the study characterizes the dose distributions produced according to the

CE

comprehensive strategy presented. Planning metrics are used to assess target coverage, dose to

outlined.

AC

normal tissue, and plan quality. Recommendations for dose constraints and minor variations are

Methods and Materials

Patient Characteristics and Contouring For this retrospective planning study, 40 patients (17 right-sided, 23 left-sided) eligible for APBI were selected and planned. Patient eligibility was based on inclusion criteria from other major clinical trials [2], [3], [4] and consensus guidelines from the major breast groups [14], [15], [16]. Common characteristics include lymph node negative and hormone receptor positive breast cancer or ductal carcinoma in situ (DCIS), with tumor size less than 2 – 3 cm, treated with breast

ACCEPTED MANUSCRIPT conserving surgery, in women at least 50 – 60 years old. Additional characteristics include negative margins by at least 2 mm, unicentric and unifocal tumors, negative lymphovascular

RI P

T

invasion, invasive ductal or other favourable histologies and HER2 not amplified tumors. All patients underwent CT simulation (Philips Big Bore, Philips, Massachusetts) in the supine

SC

position with standard wing board for immobilization. Target volume definitions were derived from existing multi-institutional trial recommendations. Gross Tumor Volume (GTV) is

NU

contoured as the lumpectomy seroma or surgical cavity visible on the planning CT scan. If

MA

present, surgical clips adjacent to the surgical cavity should be included in the surgical volumes contour. If the surgical clips are visible away from the surgical cavity and there is a normal

ED

breast tissue visible between the surgical cavity and the clips, clips should not be included in GTV. Clinical Target Volume (CTV) is defined as the GTV plus a 1 cm margin in all

PT

dimensions, trimmed to anatomical boundaries, and to exclude the pectoralis muscle, ribs,

CE

sternum, chest wall and to be 5 mm from the skin. Planning Target Volume (PTV) is defined as the CTV plus a 7 mm margin in all dimensions. Dose evaluation volume (DEV) is defined by the

AC

PTV trimmed back 5 mm from chestwall and skin. Contoured organs at risk (OARs) include ipsilateral and contralateral breast, ipsilateral and contralateral lung, heart, liver, and thyroid. For OAR contouring, ipsilateral chestwall volume includes pectoralis muscles, chestwall muscles and ribs and it should extend at least 2 cm superiorly and inferiorly from the GTV. Ipsilateral and contralateral breast volumes are contoured according to the Radiation Therapy Oncology Group (RTOG) Breast Cancer Atlas for Radiation Therapy Planning and includes apparent CT glandular breast tissue and clinically referenced breast at the time of the CT simulation, cranially extending to the level of second rib insertion, medially to the sternal-rib junction, inferiorly to the level of the loss of CT apparent

ACCEPTED MANUSCRIPT breast tissue, laterally to the mid axillary line. Heart is contoured as per RTOG [17] with the superior most contour at the inferior aspect of the left pulmonary artery and the inferior most

T

contour at the level of diaphragm. Thyroid gland is contoured to include all thyroid tissue visible

RI P

on the planning CT scan.

SC

Treatment Planning and Clearance Tables

NU

To quantify the relationship between the gantry, couch, and patient positions, a conservative patient setup was simulated and clearance measurements were made. This patient simulation

MA

involved a conservatively exaggerated arm/elbow position simulated in the wing board immobilization device and being cognizant of the possibility of large body habitus along the

ED

length of the couch. On a TrueBeam™ linear accelerator (Varian Medical Systems, California)

PT

with Exact IGRT couch, in IEC 61217 coordinates, and laser guard turned off, clearance was measured for couch verticals of 5 through 25 cm in increments of 5 cm and all couch and gantry

CE

combinations in increments of 5 degrees. Couch lateral positions from isocentre of 5, 10, and 15

AC

cm were included. These results were tabulated for all permutations of couch lateral, couch vertical, couch and gantry angle combinations. In the relevant range for breast patients, superior/inferior shifts did not impact clearance. Both couch vertical and lateral shifts directly describe the position of the seroma relative to the CT origin and, therefore, are the parameters impacting gantry clearance. The couch shifts directly define the patient position relative to the linear accelerator, whereas arm/elbow position and body habitus can be in any number of possible orientations. The majority of beam arrangements are limited by couch and gantry interactions, which is the reason seroma location is the primary limiting factor. The minority of beam arrangements are impacted by patient body habitus or arm/elbow position, so were streamlined by a conservative patient simulation.

ACCEPTED MANUSCRIPT Each seroma location is characterized in a set of four 2D tables; one table defines the clearance for each off-axis tangent beam orientation (e.g. superior medial oblique, inferior medial oblique,

T

superior lateral oblique, inferior lateral oblique). This exhaustive set of clearance tables is not

RI P

shown as it was measured to the clearance limitations of the linear accelerator suite referenced above. In Figure 1(a), a specific example of one of the four (inferior medial oblique) clearance

SC

tables for a left-sided patient with lateral seroma location is shown. In addition, in Figure 1(b),

NU

we show a generalized clearance table that includes the allowable range for all seroma locations (based on couch verticals and laterals) that could be utilized to recreate and validate centre

MA

specific tables. The clearance chart shows couch and gantry arrangements that are permissible (green) and impermissible (red), as well as a region that should be characterized on a centre-

ED

specific basis (orange). The orange region is used to present a compressed version that

PT

incorporates all seroma locations. It depicts the range of potentially allowable beam arrangements, defined by the couch vertical and lateral. The patient’s anterior-posterior (AP)

CE

separation, measured at the time of simulation, can be used for selection of the anterior field. The

AC

AP separation is additional information only for the anterior field because the clearance tables inherently include this information for the medial and lateral fields. The anterior field represents the case where the gantry always directly approaches the patient, so this measurement can be used for additional clearance precaution. The blue region indicates the available gantry to couch clearance and can be used with knowledge of the patient’s AP separation. This will allow a centre to use these tables as the foundation for deriving their own comprehensive arrangements to account for differences in vendor specifications on linear accelerators, centre-specific patient clearance expectations, or differences in patient immobilization. In a simple implementation of an external beam APBI program, these generalized tables could be used but plan quality may be

ACCEPTED MANUSCRIPT suboptimal and patient mocks are recommended. The comprehensive set of eight (four left and four right) generalized clearance tables are provided in Supplementary Material.

RI P

T

Optimization and Class Solutions

Using the set of clearance tables to define the solution space for inversely optimized IMRT, each

SC

patient was planned to achieve high dose conformity while minimizing doses to OARs. A

MA

that aimed to meet these planning priorities.

NU

comprehensive approach, not an exhaustive one, was taken to determine the beam arrangement

All plans utilized a 6 MV five-field non-coplanar beam strategy: four off-axis tangent fields (two

ED

medial, two lateral) and the fifth field from an anterior oblique direction significantly different than the tangent fields. A more conformal dose distribution is achieved with off-axis tangents

PT

compared to the standard for WBRT, which employ mainly on-axis tangent fields. A 3D

CE

rendering of a typical arrangement of the four off-axis tangent fields is illustrated in Figure 2(a)

AC

and the anterior field depicted in Figure 2(b). The initial beam arrangement for the off-axis tangents balanced maximizing the couch separation (45 – 65°) while selecting lateral and medial gantry angles that ensure minimal lung tissue was traversed, similar to the objective of standard tangents. Using this starting beam arrangement, the clearance charts (Figure 1(a)) were consulted to ensure the gantry and couch were in a deliverable configuration. Beam arrangements were then confirmed in beam's-eye-view (BEV) to avoid, where possible, direct beams in to OARs. At this step, if required, couch angles were adjusted to preserve the largest couch angle as this yields the greatest conformity to the target.

ACCEPTED MANUSCRIPT Plans were then inversely optimized using Varian Eclipse (Varian Medical Systems, California) treatment planning system calculation algorithm AAA version 11.0.31 and dose volume

T

optimizer version 11.0.31. With the beam angles chosen to optimize conformity, the general

RI P

optimization strategy was designed to minimize the low dose wash using standard planning constraints. All plans were renormalized such that 95% of the dose evaluation volume (DEV)

SC

was covered by 98% of the dose.

NU

Dose Reporting and Metrics

MA

To be consistent with the other major APBI clinical trials, normal tissue dose metrics were measured as an indicator of plan quality. Table 1 includes comparison of the planning constraints

ED

used in three multi-institutional APBI clinical trials [2], [3], [4]. For this study, the conformity

PT

index was used to score the conformity of the high dose region to the target and is defined as the 95% isodose volume divided by the target volume. The homogeneity was also assessed and

CE

reported as the average and range of the D2%.

AC

The DEV is defined as the PTV trimmed from the lung-chestwall and skin-air interface by 5 mm. In general, DEV volumes are trimmed more when the seroma volume is near midline and in proximity to both interfaces and/or when the breast volume is small. Consequently, the DEV-toPTV ratio is an indicator of the seroma locations proximity to midline and may predict plan quality [18]. A quadrant analysis was performed to determine if there were systematic differences in beam arrangements based on seroma location. The quadrants were defined by the geometrical centre of the breast contour compared to the geometrical centre of the seroma contour.

ACCEPTED MANUSCRIPT Results and Discussion

T

Class Solutions

RI P

The recommended class solutions are presented for left- and right-sided breast seroma locations (Table 2). The median and range of gantry and couch angles are presented, as well as the median

SC

couch separation of all fields. The lateral fields are constrained by entrance through the patient

NU

arm and exit through the contralateral breast, often leading to a smaller couch angle separation. Class solutions by quadrant were investigated but no trends were observed. To achieve

MA

meaningful quadrant-specific recommendations, the differences observed between quadrants would need to either result in dosimetrically or clinically relevant endpoints/outcomes. Neither

ED

goal is achievable in any realistic patient population based on unequal quadrant accrual in the

PT

breast cancer population and the statistical implications of 8 separate quadrant possibilities [19].

CE

The class solutions presented are intended for implementation with free-breathing patients. The vast majority of centres performing APBI do not apply the use of motion management in this

AC

cohort. Studies have reported that respiratory amplitudes in this cohort are approximately 2 mm [20], [21] and, in accordance with AAPM guidelines, respiratory motion management is not generally necessary unless amplitudes exceed 5 mm [22]. Moreover, follow-up studies demonstrated that respiratory motion in APBI patients did not degrade target coverage unless breathing amplitude exceeded 10 mm [23]. Patient setup uncertainty will impact dose delivery to the CTV depending on verification imaging modality, the PTV margin selected, and patient body habitus. The PTV margin for the APBI cohort is typically between 5 and 10 mm, [2], [3], [4], [6], [24], [25], and should depend on a centre’s ability to confidently setup patients. Ultimately, the dose delivered to the CTV is

ACCEPTED MANUSCRIPT reflected in the margin selected for the PTV and the setup method. Cox et al., quantified the change in dose to the ipsilateral breast depending on PTV margin, resulting in a 6% to 7%

T

increase per 5 mm increment [26]. Because the margin selected can vary from centre to centre,

RI P

some variation in the planning dose to the ipsilateral breast and adjacent organs at risk should be

SC

expected.

NU

Dose Reporting

In general, the normal tissue metrics aligned with dose levels similar to the multi-institutional

low dose regions.

MA

APBI trials. Specifically, ipsilateral breast constraints were chosen to capture both the high and Otherwise, the metrics were chosen to describe typical DVH curve

ED

characteristics of those organs. Table 3 reports the median and range of plan quality metrics as

PT

well as recommends dose constraints and minor variations. The recommendations were derived by enumerating the dose cut-offs which would be satisfied by 83% (one standard deviation above

CE

the mean) of the patients planned. Minor variations contain the remaining patient population,

AC

while ensuring that no recommendation exceeded the constraints defined and under clinical investigation by the multi-institutional trials. Without knowledge of the clinical consequence of the recommendations of this study, it is prudent to at least match the criteria outlined by the multi-institutional trials. The dose metrics were not reported for heart in right-sided breast plans, liver in left-sided breast plans, and thyroid because the dose calculated in these cohorts were zero. The right-sided liver doses were generally near zero for superior seroma locations. Consequently, there were only a small number of patients with inferior seroma locations and these constraints and variations should serve as a guide to achievable dosimetry. As an additional indicator of plan quality and

ACCEPTED MANUSCRIPT target coverage homogeneity, the maximum D2% was 104.9% of the prescription dose for the cohort of 40 patients. Although the multi-institutional trials used a maximum dose constraint for

T

the contralateral breast, the recommendations in this work presented D2% criteria to adhere ICRU

RI P

dose reporting convention. Therefore, all plans met the ICRU83 prescription criteria [24].

SC

Dose constraints and minor variations are, in general, more stringent in comparison to the other multi-institution trials. This is especially evident in the ipsilateral lung and breast constraints,

NU

where analogous constraints are improved by 5 to 15% and 15 to 25%, respectively. This

MA

represents a very large reduction in low dose wash in the ipsilateral lung as well as a large overall dose reduction in dose delivered to the ipsilateral breast. To put this in the context of the

ED

other multi-institutional trials, this 5-field IMRT planning strategy yields only 1/40 minor deviations compared to the 32/42 in the RTOG 0319 feasibility study. As well, the Italian trial

PT

reported comparable dosimetry, the focus of the work was not to report on a planning method to

CE

reproduce the results. Consequently, this 5-field class solution approach is not the first attempt to report improvements in IMRT APBI dosimetry but this does represent a comprehensive and

AC

reproducible planning strategy that led to non-trivial improvement to important normal tissues, which is critical knowledge for centres to adopt their own APBI program. The standard of care alternative to APBI for early-stage breast cancer is WBRT. For context, a 10-patient cohort of patients treated with WBRT was assessed to compare the proposed APBI dose constraints. In all cases, the dose as a percentage of the prescription is improved for the APBI cohort (Supplementary Material).

ACCEPTED MANUSCRIPT Anatomy specific plan quality Only strongly delineating trends were observed for left-sided heart dose and right-sided liver

RI P

T

dose. These results were expected when compared to dose constraints from other clinical trials. For each patient, the DEV-to-PTV was calculated and plotted against dose metrics for both target

SC

coverage and normal tissues. The median (range) of the DEV-to-PTV ratio for this cohort was

NU

0.8 (0.4 – 1.0). Figure 3(a), (b), and (c) shows the three plots in which clear trends were evident based on the DEV-to-PTV ratio. The DEV-to-PTV ratio appears to be a sensitive but not specific

MA

metric as a predictor of lung dose. The DEV-to-PTV is highly predictive of conformity to the

ED

DEV. Figure 3 is intended to provide guidance on which patients may result in a minor variation. DEV conformity indices were not reported in Table 3 because of the strong correlation to DEV-

PT

to-PTV ratios. Rather on a patient-specific basis, the DEV conformity index should be assessed

CE

alongside the DEV-to-PTV ratio with knowledge of the expected result. In the case where the DEV-to-PTV ratio is small, it can be expect that the plan will have a high conformity index (1.5

AC

– 2.0).

All patients were planned with priority given to conformity index and ipsilateral breast dose, which occasionally led to planning decisions that did impact the final dosimetry of other organs at risk. The results of this can be seen by observing the high ipsilateral lung doses for one patient in Figure 3(b) and (c). The patient was re-planned with variations in priority to different metrics, where the final decision was made to accept the higher lung dose (which is still low compared to the estimated WBRT lung dose) to preserve high dose conformity. Scenarios such as this one will require clinical judgement.

ACCEPTED MANUSCRIPT Implementation Limitations The definition of beam arrangements presented here is not exhaustive or mathematically optimal.

RI P

T

Optimization would be technically feasible via computer simulation but because of the nuanced aspects of planning this patient cohort, it would be non-trivial. Phase III clinical trial results will

SC

likely characterize the relative importance of different planning dosimetry metric. This work has value added in reducing dose to normal tissues while keeping with the current goal of partial

NU

breast treatments to minimize the high dose region to the breast. The guidelines presented will

MA

allow institutions to standardize and improve their implementation of the APBI technique.

ED

Conclusions

In previous APBI publications, no available class solutions or comprehensive beam

PT

arrangements have been provided to guide planning strategy. Dosimetric results were reported

CE

describing target coverage and conformity as well as dose to OARs for 40 APBI-eligible patients. These results were used as the foundation of dose constraints and minor variations in

AC

the context of recommendations from the other multi-institutional APBI clinical trials. In this work, dose reporting recommendations are aimed at being stringent so that reproducible and highly conformal patient plans are achievable. Finally, trends in plan quality were assessed according to the ratio of DEV and PTV volumes. For both ipsilateral lung and target conformity, a smaller DEV-to-PTV ratio was indicative of a patient cohort where planning may be more challenging to meet desired constraints. The advantage of this work over existing literature is the ability to create reproducible plans that are highly conformal and minimize dose to organs at risk. These results and recommendations provide the framework for implementation of an external beam APBI program.

ACCEPTED MANUSCRIPT References

RI P

T

[1] Canadian Cancer Society's Advisory Committee on Cancer Statistics, "Canadian Cancer Statistics 2016," 2016. [Online]. Available: cancer.ca/canadian-cancer-statistics-2016-EN.pdf. [Accessed 9 February 2017].

SC

[2] I. Olivotto, T. Whelan and S. Parpia, "Interim cosmetic and toxicity results from RAPID: A randomized trial of accelerated partial breast irradiation using three-dimensional conformal external beam radiation therapy," Journal of Clinical Oncolgoy, vol. 31, no. 32, pp. 4038-4045, 2013.

MA

NU

[3] T. B. Julian, J. P. Costantino, F. Vicini, J. White, K. A. Winter, D. W. Arthur, R. R. Kuske, R. Rabinovitch, W. J. Curran and N. Wolmark, "Early Toxicity Results with 3-D Conformal Externa Beam Therapy (CEBT) from teh NSABP B-39/RTOG 0413 Accelerated Partial Breast Irradiation (APBI) Trial," International Journal of Radiation Oncology, Biology, Physics, vol. 81, no. 2, p. S7, 2011.

PT

ED

[4] L. Livi, I. Meattini, L. Marrazzo, G. Simontacchi, S. Pallotta, C. Saieva, F. Paiar, V. Scotti, C. De Luca Cardillo, P. Bastiani, L. Orzalesi, D. Casella, L. Sanchez, J. Nori, M. Fambrini and S. Bianchi, "Accelerated partial breast irradiation using intensity-modulated radiotherapy versus whole breast irradiation: 5-year survival analysis of a phase 3 randomized controlled trial," European Journal of Cancer, vol. 51, no. 4, pp. 451-463, 2015.

CE

[5] B. Hickey, M. Lehman, D. Francis and A. See, "Partial Breast Irradiation for Early Breast Cancer," Cochrane Database of Systematic Reivews, no. 7, 2016.

AC

[6] R. Rabinovitch, J. Moughan, F. Vicini, H. Pass, J. Wong, S. Chafe, I. Petersen, D. Arthur and J. White, "Long-Term Update of NRG Onology RTOG 0319: A Phase 1 and 2 Trial to Evaluate 3Dimensional Conformal Radiation Therapy Confined to the Region of the Lumpectomy Cavity for Stage I and II Breast Cancinoma," International Journal of Radiation Oncology, Biology, Physics, vol. 96, no. 5, pp. 1054-1059, 2016. [7] K. L. Baglan, M. B. Sharpe, D. Jaffray, R. C. Frazier, J. Fayad, L. L. Kestin, V. Remouchamps, A. A. Martinez, J. Wong and F. A. Vicini, "Accelerated Partial Breast Irradiation using 3D Conformal Radiation Therapy (3D-CRT)," vol. 55, no. 2, pp. 302-311, 2003. [8] A. Lewin, R. Derhagopian, K. Saigal, J. Panoff, A. Abitbol, J. Wieczorek, V. Mishra, I. Reis, A. Ferrell, L. Moreno and C. Takita, "Accelerated partial breast irradiation is safe and effetctive using intensity-modulated radiation therapy in selected early-stage breast cancer," International Journal of Radiation Oncology, Biology, Physics, vol. 82, no. 5, pp. 2104-2110, 2012. [9] J.-J. Qui, Z. Chang, J. Horton, Q.-R. Jackie, S. Yoo and F.-F. Ying, "Dosimetric comparison of 3D conformal, IMRT, and V-MAT techniques for accelerated partial-breast irradiation (APBI)," Medical Dosimetry, vol. 39, pp. 152-158, 2014.

ACCEPTED MANUSCRIPT [10] M. Essers, S. Osman, S. Hol, T. Donkers and P. Poortmans, "Accelerated partial breast irradiation (APBI): Are breath-hold and volumetric radiation techniques useful?," Acta Oncologica, vol. 53, pp. 788-794, 2014.

SC

RI P

T

[11] D. Peterson, P. Truong, S. Parpia, I. Olivotto, T. Berrang, D. Kim, I. Kong, I. Germain, A. Nichol, M. Akra, I. Roy, M. Reed, A. Fyles, T. Trotter, F. Perera, S. Balkwill, S. Lavertu, E. Elliott, J. Julian, M. Math, M. Levine and T. Whelan, "Predictors of Adverse Cosmetic Outcome in the RAPID Trial: An Exploratory Analysis," International Journal of Radiation, Oncology, Biology, vol. 91, no. 5, pp. 968-976, 2015.

NU

[12] S. J. Becker, "Collision indicator charts for gantry-couch position combintations with Varian linacs," Journal of Applied Clinical Medical Physics, vol. 12, no. 3, pp. 16-22, 2011.

MA

[13] S. J. Becker, W. Culberson and R. T. Flynn, "Collision indicator charts for gantry-couch position combinations for Siemens ONCOR and Elekta Infinity linacs," Journal of Clinical Applied Medical Physics, vol. 14, no. 5, pp. 278-283, 2013.

PT

ED

[14] B. D. Smith, D. W. Arthur, T. A. Buchholz, B. G. Haffty, C. A. Hahn, P. H. Hardenbergh, T. B. Julian, L. B. Marks, D. A. Todor, F. A. Vicini, T. J. Whelan, J. White, J. Y. Wo and J. Harris, "Accelerated Partial Breast Irradiation Consensus Statement From the American Society for Radiation Oncology (ASTRO)," International Journal of Radiation Oncology, Biology, Physics, vol. 74, no. 4, pp. 987-1001, 2009.

AC

CE

[15] C. Polgar, E. Van Limbergen, R. Potter, G. Kovacs, A. Polo, J. Lyczek, G. Hildebrandt, P. Niehoff, J. L. Guinot, F. Guedea, B. Johansson, O. J. Ott, T. Major and V. Stmad, "Patient selection for accelerated partial-breast irradiation (APBI) after breast-conserving surgery: Recommendations of the Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) breast cancer working group ba," Radiothearpy and Oncology, vol. 94, no. 3, pp. 264-273, 2009. [16] The American Society of Breast Surgeons, "Consensus Statement for Accelerated Partial Breast Irradiation," 15 August 2011. [Online]. Available: https://www.breastsurgeons.org/new_layout/about/statements/PDF_Statements/APBI.pdf. [Accessed 30 June 2016]. [17] M. Feng, J. M. Moran, T. Koelling, A. Chughtai, J. L. Chan, L. Freedman, J. A. Hayman, R. Jagsi, S. Jolly, J. Larouere, J. Soriano, R. Marsh and L. J. Pierce, "Development and validation of a heart atlas to study cardiac exposure to radiation following treatment for breast cancer," International Journal of Radiation Oncology, Biology, Physics, vol. 79, no. 1, pp. 10-18, 2011. [18] S. Quirk, L. Conroy and W. L. Smith, "Accounting for respiratory motion in partial breast intensity modulated radiotherapy during treatment planning: A new patient selection metric," European Journal of Cancer, vol. 50, no. 11, pp. 1872-1879, 2014.

ACCEPTED MANUSCRIPT [19] J. Bao, K. Yu, Y. Jiang, Z. Shao and G. Di, "The effect of laterality and primary tumor site on cancer-specific mortality in breast cancer: a SEER population-based study," Public Library of Science one, vol. 9, no. 4, p. e94815, 2014.

RI P

T

[20] S. Quirk, L. Conroy and W. L. Smith, "External respiratory motion analysis and statistics for patients and volunteers," Journal of Applied Clinical Medical Physics, vol. 14, no. 2, pp. 90-101, 2013.

SC

[21] C. Glide-Hurst, M. Shah, R. Price, C. Liu, J. Kim, M. Mahan, C. Fraser, I. Chetty, I. Aref, B. Movas and E. Walker, "Intrafraction Variability and Deformation Quantification in the Breast," International Journal of Radiation Oncology, Biology, Physics, vol. 91, no. 3, pp. 604-11, 2015.

MA

NU

[22] P. Keall, G. Mageras, J. Balter, R. Emery, K. Forster, S. Jiang, J. Kapatoes, D. Low, M. Murphy, B. Murray, C. Ramsey, M. Van Herk, S. Vedam, J. Wong and E. Yorke, "The managemenr of respiratory motion in radiation oncology report of AAPM Tast Group 76," Medical Physics, vol. 33, no. 10, pp. 3874-3900, 2006.

ED

[23] S. Quirk, L. Conroy and W. Smith, "When is respiratory management necessary for partial breast intensity modulated radiothearpy: A respiratory amplitude escalation treatment planning study.," Radiotherapy and Oncology, vol. 112, no. 3, pp. 402-6, 2014.

PT

[24] S. Shah, A. Kyrillos, K. Kuchta, H. Habib, M. Tobias, V. Raghavan, A. Shaikh, W. Bloomer, C. Pesce and K. Yao, "A single institution retrospective comparision study of locoregional recurrence after accelerated partial breast irradiation using external beam fractionation compared with whole breast irradiation with 8 years of follow up," Annals of Surgical Onology, 2017.

AC

CE

[25] N. Meszaros, T. Major, G. Stelczer, Z. Zaka, E. Mozsa, D. Oukancsik, Z. Takacsi-Nagy, J. Fodor and C. Polgar, "Implentation of image-guided intensity-modulated accelerated partial breast irradiation: Three-year results of a phase 2 clinical study," Strahlentherapie und Onkologie, vol. 193, pp. 70-79, 2017. [26] B. Cox, K. Horst, S. Thornton and F. Dirbas, "Impact of increasing margin around the lumpectomy cavity to define the planning target volume for 3D conformal external beam accelerated partial breast irradiation," Medical Dosimetry, vol. 32, no. 4, pp. 254-262, 2007. [27] "ICRU Report 83: Prescribing, Recording, and Reporting Photon-Beam Intensity-Modulated Radiation Therapy (IMRT)," Journal of the ICRU, vol. 10, no. 1, 2010.

ACCEPTED MANUSCRIPT Figure Captions Figure 1: (a) Allowable gantry and couch arrangements are represented by green squares on the

RI P

T

clearance table. The yellow boxes indicate a transition region that represents a potential physical collision. Red boxes indicate likely collision. The anterior field clearance is specified by the blue

SC

boxes. (b) Is a generalized version of the clearance chart shown in (a) with orange boxes indicating the regions that should be evaluated on an institutional-specific basis by patient mock

NU

or simulation.

MA

Figure 2: (a) A typical beam arrangement of the four off-axis tangents. (b) A typical placement

ED

of the anterior field.

PT

Table Captions

Figure 3: The trend in DEV-to-PTV ratio as a function of (a) DEV Conformity Index and (b)

CE

lung V10% and (c) lung V30%. In all cases, as the DEV-to-PTV ratio decreases, the dose to lung

AC

and DEV CI worsens.

Table 1: Large multi-institutional APBI clinical trial dose constraints. Table 2: Class solution for five-field beam arrangement in APBI are presented for left- and rightsided breast seroma locations; median (range) for gantry and couch angles and the median couch angle separation for all fields. Table 3: Median values and ranges reported for dose metrics pertaining to PTV and normal tissues.

ACCEPTED MANUSCRIPT Table 1: Large multi-institutional APBI clinical trial dose constraints RAPID [2]

RTOG 0413 [3]

Italian Trial [4]

(DEV) V95% Rx = 100%

(DEV) V90% Rx = 90%

(PTV) V95% Rx = 100%

38.5 Gy/10 BID

38.5 Gy/10 BID

30 Gy/5 over 10 days

RI P

T

Target and prescription

Ipsilateral Lung V10% Rx < 20%

V30% Rx < 15%

V10Gy < 20%

SC

V30% Rx < 10% V50% Rx < 50 - 60%

V50% Rx < 60%

V95% Rx < 25 - 35%

V100% < 35%

Heart (left-sided) V5% < 10 - 15% Rx

V5% Rx < 40%

MA

Contralateral Breast

NU

Ipsilateral Breast

Dmax < 3% Rx

AC

CE

PT

ED

Dmax < 3% Rx

V15Gy < 50% (uninvolved)

V3Gy < 10% Dmax < 1 Gy

ACCEPTED MANUSCRIPT Table 2: Class solution for five-field beam arrangement in APBI are presented for left- and right-sided breast seroma locations; median (range) for gantry and couch angles and the median couch angle separation for all fields. Left

Right

Gantry

Couch

Gantry

Medial Superior

325° (305 - 350)°

330° (315 - 350)°

35° (30 - 45)°

Medial Inferior

315° (295 - 335)

30° (15 - 75)°

45° (25 - 55)°

RI P

60° (30 – 115)°

Couch Angle Separation 135° (105 - 150)

30° (0 - 30)°

Lateral Inferior

120° (95 - 150)

340° (330 - 345)° 45° (20 – 60)°

NU

270° (40 - 270)°

CE

PT

ED

MA

325° (35 - 340)

AC

Anterior

Couch 30° (15 - 40)° 330° (325 - 345)° 55° (30 – 75)°

230° (210 - 240)°

330° (330 - 345)°

240° (220 - 250)°

20° (15 - 30)°

SC

Lateral Superior

Couch Angle Separation

T

Field

35° (20 - 320)°

50° (35 – 55)° 270° (85 - 295)°

ACCEPTED MANUSCRIPT Table 3: Median values and ranges reported for dose metrics pertaining to PTV and normal tissues. The recommendations were derived by enumerating the dose cut-offs which would be satisfied by 83% of the patients while also ensuring that no recommendations exceeded the societally accepted values provided by multi-institutional trials.

Dmean V5% Rx

0.1 1.6%

< 1.2 < 103% Rx

SC

RI P

Constraint

NU

< 15% < 5%

Minor Variation 1.2 – 1.3 103.0 – 107.0% Rx 15 – 20% 5 – 10%

< 50% < 35% < 10%

50 – 70% 35 – 45% 10 – 20%

3.1%

< 5%

5 – 10%

0.5%

< 1%

1 – 3%

2.2% 11.6%

< 3% < 15%

3 – 10% 15 – 45%

8.1% 6.4% 2.6%

MA

D2%

SD

5.8% 2.8%

ED

V5% Rx

PT

V30% Rx V50% Rx V95% Rx

CE

V10% Rx V30% Rx

Median Range PTV 1.1 0.8 – 1.3 101.4% 98.8 – 104.9% Rx Ipsilateral Lung 7.4% 0.0 – 24.5% 1.8% 0.0 – 14.5% Ipsilateral Breast 44.6% 29.0 – 66.1% 29.0% 17.8 – 40.9% 9.4% 5.6 – 15.9% Heart (left-sided) 0.3% 0.0 – 9.8% Contralateral Breast 0.4% 0.0 – 3.1% Liver (right-sided) 0.3% 0.1 – 8.9% 0.0 0.0 – 45.5%

AC

CI D2%

Recommendations

T

Reported

MA

NU

SC

RI P

T

ACCEPTED MANUSCRIPT

AC

CE

PT

ED

Figure 1

SC

RI P

T

ACCEPTED MANUSCRIPT

AC

CE

PT

ED

MA

NU

Figure 2

ED

MA

NU

SC

RI P

T

ACCEPTED MANUSCRIPT

AC

CE

PT

Figure 3