Practical Radiation Oncology (2015) 5, e283-e290
www.practicalradonc.org
Original Report
Proton partial breast irradiation in the supine position: Treatment description and reproducibility of a multibeam technique Eric A. Strom MD a,⁎, Richard A. Amos MSc b, c , Simona F. Shaitelman MD a , Matthew D. Kerr BS b , Karen E. Hoffman MD a , Benjamin D. Smith MD a , Welela Tereffe MD a , Michael C. Stauder MD a , George H. Perkins MD a , Mayankumar D. Amin MSc a , Xiaochun Wang PhD b , Falk Poenisch PhD b , Valentina Ovalle MD a , Thomas A. Buchholz MD a , Gildy Babiera MD d , Wendy A. Woodward MD PhD a a
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas c Currently at Department of Radiotherapy Physics, University College London Hospitals NHS Foundation Trust, London, United Kingdom d Department of Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas b
Received 30 May 2014; revised 2 December 2014; accepted 29 January 2015
Abstract Purpose: Proton-accelerated partial breast irradiation (APBI) is early in its developmental phase without standardized treatment parameters. We report an approach to multibeam proton APBI using a universally available supine setup and deliberate beam arrangement strategy to limit the total area of skin receiving a full dose while being robust for interfraction variation. Methods and materials: Thirty-three American Society for Radiation Oncology consensussuitable/cautionary APBI candidates were treated using a passively scattered proton beam between 2010 and 2014 to 34 Gy relative biological effectiveness in 10 fractions twice daily. All patients were immobilized in a Vac-Lok cradle, typically with the arm down, and adducted to mound the breast and facilitate multiple, optimal en face beams. Radiopaque wires were placed on the surgical scar and 3 markers separate from the scar were placed elsewhere on the breast. All markers were used for each setup and removed before treatment. Marker displacement, wire rotation, and wire displacement were recorded from 10 random patients (100 orthogonal films). A 15-mm expansion was made to the tumor bed to obtain a clinical target volume, and followed by a 5-mm skin contraction and exclusion of the chest wall. A radial planning target volume margin of 5 mm was used.
Supplementary material for this article (http://dx.doi.org/10.1016/j.prro.2015.01.010) can be found at www.practicalradonc.org. Conflicts of interest: Dr Shaitelman reports grants from Elekta, outside the submitted work. Dr Smith reports grants from Varian Medical Systems, Inc, outside the submitted work. The rest of the authors have nothing to disclose. ⁎ Corresponding author. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Box 1202, Houston, TX 77030. E-mail address: [email protected] (E.A. Strom). http://dx.doi.org/10.1016/j.prro.2015.01.010 1879-8500/© 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.
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Results: Across 100 pretreatment images, median displacement of 3 distinct skin set-up markers was 3, 4, and 3 mm. Displacement of the scar wire in the X and Y direction was 0 and 1 mm, respectively. Among 28 verification scans performed, only 1 resulted in adaptive planning because of the initial presence of an air pocket in the lumpectomy cavity that resolved spontaneously during treatment. Conclusions: APBI proton treatment using a supine approach was largely reproducible. Inter-fraction variation demonstrates 5-mm radial planning margins were adequate; however, outliers do occur and films should be reviewed critically and in real time. This technique is straightforward and could be used at any proton facility without the need for specialized equipment. © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.
Introduction Breast conservation therapy using tumor excision followed by radiation is an established best practice for patients with early-stage breast cancer. 1-8 Recent experience has used a number of approaches to postexcision radiation therapy that deliver treatment only to the sector of the breast that was initially involved. These accelerated partial breast irradiation (APBI) techniques 9 include intracavitary radiation devices (brachytherapy), interstitial implants (also brachytherapy), intraoperative radiation techniques, and conformal linac-based external beam approaches. 10-16 With their unique dose-distribution features, protons for APBI are obvious tools to explore because they provide highly contained radiation with minimal dose outside the target region. Several institutions have reported initial clinical results of proton APBI. 17-19 A major drawback of protons is that passively scattered beams can have little or no skin sparing for superficial targets—delivering close to 100% of the prescribed dose to the skin for each beam. Indeed, the first clinical experience reported unexpected rates of skin toxicity using an approach in which only 1 field was treated per fraction. 20 Encouragingly, another group reported excellent cosmetic outcomes using a distinct multibeam technique, but in the prone position with a custom table. 21 We have previously reported a dosimetric exploration of a supine multibeam configuration that could deliver skin sparing with protons comparable to 3-dimensional conformal radiation therapy plans. 22 This study describes our initial experience with this proton APBI planning and treatment delivery technique and reproducibility using the supine approach.
Methods and materials Thirty-three American Society for Radiation Oncology consensus suitable/cautionary APBI candidates were treated between 2010 and 2014 using a passive scattered proton beam. The institutional review board approved this prospective protocol and all patients signed patientspecific consent before treatment. The protocol is registered with the National Cancer Institute as NCI2011-01102. To be eligible, patients were required to have
unifocal stage 0-I-II breast cancers ≤ 3 cm in size treated with lumpectomy. Surgically free margins were required and the target lumpectomy cavity must have been clearly delineated. Patients with multicentric carcinomas, 3 or more positive lymph nodes, nonepithelial breast malignancies, and those treated with initial chemotherapy were excluded.
Positioning All patients were immobilized supine in a Vac-Lok (Civco Medical Solutions) cradle, typically rotated slightly onto their contralateral side and with the ipsilateral arm down and adducted. Patients with very lateral tumor beds were treated with the arm abducted, still making every attempt to position the patient in such a way as to mound rather than stretch or flatten the breast. Optimally, proton beams are delivered perpendicularly to the skin surface so the tumor is at a consistent depth of tissue along the beam’s pathway. As in supplemental Fig 1A, tangential beams are susceptible to underdosing with relatively minor changes in positioning. 23 Further, with the arm down, it is easier to avoid clipping the anatomy on the scan field of view. Clipping creates image reconstruction artifacts throughout the computed tomography (CT) data (supplemental Fig 2), which has been shown to alter the proton range at the 50% distal isodose line by 2-3 mm; this is as much as a typical distal margin even when remote to the target. 24 In many cases, the arm and positioning can be used to mound the breast to create greater opportunity for en face arrangements (Fig 1). As in Fig 2, a radiopaque wire was placed on the surgical scar and markers were placed on the nipple and in at least 2 other locations on the breast separate from the scar to identify the breast contour. The wire displacement relative to the reference was measured 1 cm from the center of the wire in the X and Y directions for each anteroposterior film for each patient. Vector sums of X and Y displacements were recorded and the rotation calculated for each film. Further, the shortest displacement among the 3 markers including the nipple on the reference and image guided radiation therapy images was recorded for each film. All markers were used for orthogonal kV x-ray image guided setup before each treatment and were removed before proton beam delivery to avoid perturbation.
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Figure 1 Positioning. Sequential setup in the same patient illustrates the deliberate mounding of the breast with the arm down (A) versus the flattening of the upper inner quadrant (surgical bed) with the arm abducted (B).
Treatment planning was performed using Eclipse (Varian Medical Systems, Palo Alto, CA). The Hounsfield units of the radiopaque markers were overridden with air density for proton dose and range calculation. Marker displacement, wire rotation, and wire displacement at each treatment were recorded and assessed from 10 random patients (100 orthogonal films). Detailed setup information was presented for discussion as an e-poster at American Society for Radiation Oncology’s 2014 annual meeting. 25
Planning Target volume definitions and expansions are similar to those used in National Surgical Adjuvant Breast and Bowel Project B-39 for 3-dimensional conformal external beam APBI. However, because of the increased dose
conformality with protons, the volume of nontarget breast tissue treated is low 23,26,27 and constraints related to the portion of whole breast treated were never approached. The clinical target volume (CTV) was obtained initially by a 15-mm expansion on the tumor bed inclusive of clips and seroma. This volume was then contracted 5 mm from the skin and edited to exclude the chest wall, including the muscle. A radial planning target volume (PTV) margin of 5 mm was used. Proximal and distal beam-specific margins were 3.5% of the range + 1 mm from the CTV. Beam-specific range compensator smearing radii were calculated using 3% of the range and 5 mm positional uncertainty summated in quadrature. The prescribed dose was 34 Gy (relative biological effectiveness) in 10 fractions twice daily over a 1-week period, with a minimum 6-hour interfraction interval. Our goals for
Figure 2 Setup reproducibility. Ten anteroposterior image guided radiation therapy films from 10 randomly selected patients were reviewed for setup variability.
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dose constraints followed the guidelines of National Surgical Adjuvant Breast and Bowel Project B-39 and were met in all cases. Although not specifically required by the protocol, repeat CT scans were taken in the treatment position no later than the second fraction and were used to assess setup reproducibility and the effect of internal anatomical changes on the dose distribution. Thermoluminescent dosimeter measurements within the beam overlap on skin were obtained for the first 7 patients. Clinical evaluations were performed before and during radiation therapy, 2 and 6 weeks after completion of radiation therapy, and every 6 months thereafter. Acute and late toxicities were assessed using the Commom Terminology Criteria for Adverse Events criteria, version 4. 28
Statistics Descriptive statistics were generated using IBM SPSS Statistics, version 21.
Results All plans were free of CT artifacts related to clipping. Of 28 cases in which verification scans were performed (supplemental Fig 3), 1 treatment plan was adapted (supplemental Fig 3). This patient had an air pocket in the lumpectomy cavity at initial planning, which resolved spontaneously during treatment, altering the dose distribution. To expedite implementation of the adapted plan, field-defining apertures and range compensators were unchanged. To adapt the plan the range and spread-out Bragg peak of each beam was adjusted using the proton delivery system (Probeat, Hitachi America Limited, Inc, Tarrytown, NY). Monitor units were adjusted to account for the change in range shifter and spread-out Bragg peak factors. 29 Maximum thermoluminescent dosimeter dose ranged from 74% to 105% of the prescription (average, 97%). Median skin area included in all beams was 13 cm 2
Table 1
(standard deviation ± 11). The median portion of the heart receiving 5% of the prescription was 0%.
Reproducibility of treatment Setup variability summary statistics (across 100 measurements) are presented in Table 1. The summary statistics for individual patients are presented in Table 2. All values N 1 cm are highlighted in red. In general, the setup was adjusted to split the difference of any displacement across the multiple setup points, with more priority given to alignment of the scar wire because this closely associated with the tumor bed. Nonscar markers were generally permitted to have greater displacement. The radial PTV was 5 mm. Five patients (patients B, F, G, H, and I) had N 75% of measurements that were ≤ 5 mm for each displacement measurement (wire and markers). In 1 patient (E), the 75th percentile of 1 displacement measurement was N 5 mm. In 3 patients (patients A, C, and J), the 75th percentile of 2 displacement measurements were N 5 mm. The averages of these summary measurements per patient are presented in Table 3 to provide an overview across patients. Percentiles for individual patient data demonstrating variation N 1 cm are generally uncommon within 10 treatments. There was no discernable pattern among patients (initial cohorts vs later) or within-treatment fractions for any single patient (first half vs second half). Worst-case analysis was performed on the treatment plan for the patient with the largest setup displacement (patient A). This revealed that 34 Gy covered 96% of the CTV under this suboptimal circumstance. A graph of the robustness analysis performed for this patient is shown in supplemental Fig 4.
Discussion Adjuvant radiation therapy after breast-conserving surgery is a standard alternative for most patients with early-stage breast cancer that results in high success rates with infrequent complications. 5,6 The past decade has
Interpatient data summary (100 measurements across 10 patients) Rotation (°) Nipple marker (cm) Marker 2 (cm) Marker 3 (cm) Delta X (cm) Delta Y (cm) Vector XY (cm)
Mean Median Minimum Maximum Percentiles 25th 50th 75th
0.09 0.07 0.00 0.32 0.04 0.07 0.13
0.36 0.33 0.02 0.99 0.24 0.33 0.45
0.46 0.42 0.03 1.50 a 0.26 0.42 0.58
0.40 0.32 0.05 1.70 0.20 0.32 0.48
0.00 − 0.02 − 0.83 1.10 − 0.22 − 0.02 0.19
− 0.07 − 0.05 − 0.82 0.78 − 0.18 − 0.05 0.09
0.36 0.30 0.00 1.12 0.17 0.30 0.53
Rotation, delta X, delta Y, and vector XY refer to displacement of the wire placed on the lumpectomy scar taken 1 cm from the center of the wire. a Boldface type indicates values N 1 cm.
Practical Radiation Oncology: July-August 2015 Table 2 Patient A Mean Median Minimum Maximum Percentiles
Patient B Mean Median Minimum Maximum Percentiles
Patient C Mean Median Minimum Maximum Percentiles
Patient D Mean Median Minimum Maximum Percentiles
Patient E Mean Median Minimum Maximum Percentiles
Patient F Mean Median Minimum Maximum Percentiles
Patient G Mean Median Minimum Maximum Percentiles
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Intrapatient data summary Statistics
Rotation (°)
Nipple marker (cm)
Marker 2 (cm)
Marker 3 (cm)
Delta X (cm)
Delta Y (cm)
Vector XY (cm)
25th 50th 75th
0.09 0.08 0.00 0.23 0.04 0.08 0.14
0.54 0.51 0.30 0.89 0.41 0.51 0.65
0.45 0.48 0.20 0.75 0.29 0.48 0.54
0.77 0.63 0.30 1.70 a 0.47 0.63 1.06
0.15 − 0.02 − 0.40 1.10 − 0.11 − 0.02 0.45
0.03 − 0.02 − 0.17 0.26 − 0.08 − 0.02 0.19
0.36 0.24 0.09 1.12 0.14 0.24 0.48
25th 50th 75th
0.17 0.16 0.04 0.32 0.06 0.16 0.28
0.33 0.33 0.20 0.43 0.25 0.33 0.42
0.36 0.33 0.25 0.62 0.26 0.33 0.41
0.31 0.28 0.17 0.81 0.20 0.28 0.32
− 0.29 − 0.35 − 0.74 0.41 − 0.54 − 0.35 − 0.08
− 0.23 − 0.19 − 0.58 0.08 − 0.39 − 0.19 − 0.07
0.52 0.54 0.34 0.75 0.39 0.54 0.62
25th 50th 75th
0.05 0.04 0.01 0.10 0.03 0.04 0.07
0.52 0.50 0.10 0.99 0.22 0.50 0.87
0.53 0.44 0.03 1.50 0.31 0.44 0.67
0.45 0.43 0.12 1.15 0.27 0.43 0.51
0.12 0.13 − 0.30 0.64 − 0.23 0.13 0.35
− 0.19 − 0.18 − 0.58 0.08 − 0.30 − 0.18 − 0.11
0.36 0.31 0.11 0.86 0.21 0.31 0.44
25th 50th 75th
0.10 0.10 0.04 0.19 0.04 0.10 0.14
0.64 0.62 0.25 1.25 0.40 0.62 0.82
0.53 0.59 0.10 0.81 0.35 0.59 0.76
− 0.37 − 0.43 − 0.83 0.07 − 0.56 − 0.43 − 0.12
− 0.05 − 0.05 − 0.69 0.78 − 0.48 − 0.05 0.25
0.56 0.58 0.03 0.95 0.36 0.58 0.78
25th 50th 75th
0.03 0.03 0.00 0.05 0.02 0.03 0.04
0.25 0.24 0.13 0.37 0.15 0.24 0.36
0.84 0.84 0.26 1.37 0.49 0.84 1.24
0.34 0.30 0.12 0.93 0.15 0.30 0.45
0.33 0.26 0.07 0.69 0.15 0.26 0.52
0.04 0.03 − 0.14 0.24 − 0.04 0.03 0.13
0.36 0.29 0.13 0.70 0.18 0.29 0.52
25th 50th 75th
0.06 0.05 0.00 0.17 0.03 0.05 0.09
0.27 0.26 0.05 0.50 0.19 0.26 0.41
0.34 0.27 0.16 0.74 0.20 0.27 0.49
0.30 0.28 0.11 0.84 0.17 0.28 0.33
− 0.06 − 0.10 − 0.31 0.08 − 0.13 − 0.10 0.06
0.01 0.01 − 0.39 0.22 − 0.07 0.01 0.15
0.18 0.13 0.07 0.50 0.10 0.13 0.23
25th 50th 75th
0.13 0.12 0.06 0.23 0.09 0.12 0.17
0.41 0.45 0.20 0.63 0.29 0.45 0.49
0.32 0.36 0.07 0.53 0.20 0.36 0.44
0.36 0.33 0.09 0.84 0.23 0.33 0.46
− 0.11 − 0.14 − 0.27 0.12 − 0.25 − 0.14 0.02
− 0.16 − 0.15 − 0.39 0.02 − 0.24 − 0.15 − 0.06
0.23 0.24 0.02 0.47 0.12 0.24 0.31
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Table 2 (continued) Patient A Patient H Mean Median Minimum Maximum Percentiles
Patient I Mean Median Minimum Maximum Percentiles
Patient J Mean Median Minimum Maximum Percentiles
Statistics
Rotation (°)
Nipple marker (cm)
Marker 2 (cm)
Marker 3 (cm)
Delta X (cm)
Delta Y (cm)
Vector XY (cm)
25th 50th 75th
0.06 0.04 0.00 0.16 0.02 0.04 0.09
0.30 0.31 0.11 0.61 0.15 0.31 0.36
0.26 0.26 0.07 0.70 0.11 0.26 0.32
0.23 0.24 0.06 0.36 0.16 0.24 0.31
0.10 0.10 − 0.25 0.71 − 0.15 0.10 0.24
0.07 0.12 − 0.36 0.56 − 0.15 0.12 0.22
0.32 0.29 0.00 0.72 0.22 0.29 0.41
25th 50th 75th
0.07 0.07 0.00 0.19 0.02 0.07 0.11
0.35 0.35 0.17 0.51 0.28 0.35 0.42
0.38 0.39 0.23 0.60 0.29 0.39 0.47
0.29 0.27 0.05 0.69 0.15 0.27 0.41
0.09 0.03 − 0.33 0.59 − 0.11 0.03 0.35
0.02 0.04 − 0.47 0.51 − 0.13 0.04 0.17
0.32 0.29 0.07 0.75 0.12 0.29 0.45
25th 50th 75th
0.11 0.08 0.03 0.23 0.05 0.08 0.18
0.22 0.24 0.02 0.37 0.12 0.24 0.33
0.51 0.50 0.22 0.75 0.45 0.50 0.61
0.32 0.32 0.22 0.42 0.22 0.32
0.03 − 0.06 -0.22 0.40 − 0.12 − 0.06 0.21
− 0.26 − 0.23 − 0.82 0.23 − 0.56 − 0.23 0.00
0.39 0.32 0.10 0.85 0.19 0.32 0.58
Rotation, delta X, delta Y, and vector XY refer to displacement of the wire placed on the lumpectomy scar taken 1 cm from the center of the wire. a Boldface type indicates values N 1 cm.
shown the widespread introduction of several alternatives to classic whole breast irradiation, including several forms of APBI. A growing body of experience demonstrates that APBI may be comparable to whole breast irradiation in properly selected low-risk stage I-II breast cancer patients. 16,30-33 Several methods to deliver APBI are available, including intracavitary and interstitial brachytherapy, linacbased external beam radiation therapy, intraoperative radiation, and, most recently, proton beam therapy. Three centers have reported their initial clinical experiences with proton APBI. The first, from the Massachusetts General Hospital, involved 19 patients with stage I breast cancer treated to 32 Gy (relative biological effectiveness) in 8 fractions on a twice-daily schedule. 20 One to 3 fields were used for the plan, but only 1 field was treated per fraction. They reported high toxicity rates and noted several treatment planning issues that may
Table 3 Patient A
have contributed to these results recommending planning modifications for future use. The second, by Chang at al 19 from the Korean National Cancer Center, details their experience with 30 patients. They also identified significant acute skin reactions seen in their first 15 patients who were treated with only a single proton beam. Modifying their approach to a multiple beam plan appeared to dramatically reduce these skin reactions. Bush et al from Loma Linda University Medical Center have published their technique for APBI with a custom prone table. 21,26 This approach also facilitates the use of multiple appositional beams by rounding the breast through prone positioning. They treated patients to 40 Gy (relative biological effectiveness) in 10 daily fractions over 2 weeks. A total of 100 patients were treated with minimal toxicity and 90% good-excellent cosmetic outcomes. Because of the limited distribution of their custom prone
Average of summary statistics across patients (ie, average of the summary statistics in Table 2) Rotation (°) Nipple marker (cm) Marker 2 (cm) Marker 3 (cm) Delta X (cm) Delta Y (cm) Vector XY (cm)
Median 0.08 Standard deviation 0.06 Maximum 0.19
0.32 0.14 0.53
0.45 0.22 0.88
0.37 0.23 0.86
0.22 0.19 0.63
0.18 0.16 0.51
0.32 0.21 0.77
Rotation, delta X, delta Y, and vector XY refer to displacement of the wire placed on the lumpectomy scar taken 1 cm from the center of the wire.
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table, the applicability of this setup and these results to other centers is unknown. A readily available (nonpatented) reproducible setup was desirable. All 3 clinical trials studying the clinical role of proton beam APBI have used similar target volumes. The margins used to create a CTV and a PTV are essentially very similar to those used for 3-dimensional conformal APBI with photons as defined by Radiation Therapy Oncology Group B-39. This arbitrary choice of expansion volumes makes comparison between these external beam techniques fairly straightforward, but is distinct from the approaches used for brachytherapy APBI. Setup precision with proton APBI is particularly important because a geographic miss can occur in both the radial and distal directions. Typical image guided radiation therapy techniques optimized for deeper body structures are not easily applied to the breast, and strategies used to guarantee treatment reproducibility have limited applicability to proton treatments. For this reason, a detailed description of a workable technique for proton APBI fills an important gap as this modality undergoes additional clinical exploration. This study describes our approach to supine proton APBI using multiple beams. The prescribed dose was chosen taking into consideration the previous doses used by other institutions and estimating an effective dose of 44 Gy for late tissue effects with an α/β of 3. None of our 33 patients treated have developed grade 3 skin reactions, suggesting that the skin dose issues identified in the prior
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MGH and National Cancer Institute–Korea reports have been overcome. Because both of these studies clearly identified these issues after treating 19 and 15 patients, respectively, careful positioning—often with the arm down—was used to optimize the apical mounding of the breast and increase the number of options for appositional beams. Also, it is our impression that using the largest available Vac-Lok cradle with deliberate support around the entire torso and particularly the ipsilateral arm and shoulder aids in the reproducibility of the setup. For most patients, a 5-mm radial margin appears adequate considering that some markers may be well outside the target volume, and an individual measurement N 5 mm may not represent a clinically significant displacement or imply that the target is displaced beyond the PTV. However, it is important to emphasize the relevance of rejecting outlier films, particularly regarding displacement of markers closely related to the target, and worst-case scenario analysis should be considered in any patient for whom the first 2 films suggest N 5-mm displacement in key markers. Proton APBI, although still in the exploratory phase, has a number of highly valued features. Dose to heart and lung can be practically eliminated and dose to rib and nontarget breast tissue can be quite low. Skin-sparing appears to be effectively achieved using multibeam approaches; however, these also introduce a greater degree of uncertainty with respect to CTV coverage. Robust treatment techniques are needed for proton APBI to fulfill
Figure 3 Cosmetic outcome examples. (Top) Cosmesis at completion of therapy, 5 weeks, 7 weeks, and 1 year in a patent with good cosmesis. Slight hyperpigmentation was evident in the field distribution at 1 year. (Bottom) Three examples of 1-year follow-up among patients with excellent cosmesis.
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its potential. This is the first detailed description of such a technique. Although the primary study endpoints cannot yet be completely assessed because accrual is still open, none of the toxicity monitoring thresholds has been crossed and no patients have developed grade 3 skin reactions (Fig 3). We describe a robust multibeam proton APBI technique that is straightforward and could be used at any proton facility without the need for specialized equipment.
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Practical Radiation Oncology: July-August 2015 14. Rabinovitch R, Winter K, Kuske R, et al. RTOG 95-17, a phase II trial to evaluate brachytherapy as the sole method of radiation therapy for stage I and II breast carcinoma—year-5 toxicity and cosmesis. Brachytherapy. 2014;13:17-22. 15. Rosenkranz KM, Tsui E, McCabe EB, et al. Increased rates of long-term complications after mammosite brachytherapy compared with whole breast radiation therapy. J Am Coll Surg. 2013;217:497-502. 16. Smith BD, Arthur DW, Buchholz TA, et al. Accelerated partial breast irradiation consensus statement from the American Society for Radiation Oncology (ASTRO). Int J Radiat Oncol Biol Phys. 2009;74:987-1001. 17. Galland-Girodet S, Pashtan I, MacDonald SM, et al. Long-term cosmetic outcomes and toxicities of proton beam therapy compared with photon-based 3-dimensional conformal accelerated partialbreast irradiation: A phase 1 trial. Int J Radiat Oncol Biol Phys. 2014;90:493-500. 18. Bush DA, Do S, Lum S, et al. Partial breast radiation therapy with proton beam: 5-year results with cosmetic outcomes. Int J Radiat Oncol Biol Phys. 2014;90:501-505. 19. Chang JH, Lee NK, Kim JY, et al. Phase II trial of proton beam accelerated partial breast irradiation in breast cancer. Radiother Oncol. 2013;108:209-214. 20. Kozak KR, Smith BL, Adams J, et al. Accelerated partial-breast irradiation using proton beams: Initial clinical experience. Int J Radiat Oncol Biol Phys. 2006;66:691-698. 21. Bush DA, Slater JD, Garberoglio C, et al. Partial breast irradiation delivered with proton beam: Results of a phase II trial. Clin Breast Cancer. 2011;11:241-245. 22. Wang X, Amos RA, Zhang X, et al. External-beam accelerated partial breast irradiation using multiple proton beam configurations. Int J Radiat Oncol Biol Phys. 2011;80:1464-1472. 23. Moon SH, Shin KH, Kim TH, et al. Dosimetric comparison of four different external beam partial breast irradiation techniques: Threedimensional conformal radiotherapy, intensity-modulated radiotherapy, helical tomotherapy, and proton beam therapy. Radiother Oncol. 2009;90:66-73. 24. Wu R, Amos R, Sahoo N, et al. Effect of CT truncation artifacts to proton dose calculation [AAPM abstract 9125]. Med Phys. 2008;35:2697. 25. Strom EA, Amos RA, Shaitelman S, et al. Prospective phase 2 proton APBI: Multibeam supine treatment is reproducible and free from acute toxicity [ASTRO abstract 1106]. Int J Radiat Oncol Biol Phys. 2014;90:S201-S202. 26. Bush DA, Slater JD, Garberoglio C, et al. A technique of partial breast irradiation utilizing proton beam radiotherapy: Comparison with conformal x-ray therapy. Cancer J. 2007;13:114-118. 27. Kozak KR, Katz A, Adams J, et al. Dosimetric comparison of proton and photon three-dimensional, conformal, external beam accelerated partial breast irradiation techniques. Int J Radiat Oncol Biol Phys. 2006;65:1572-1578. 28. National Cancer Institute. Commom Terminology Criteria for Adverse Events (CTCAE), version 4. Available at: http://evs.nci. nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_ 8.5x11.pdf. [Accessed January 5, 2015]. 29. Sahoo N, Zhu XR, Arjomandy B, et al. A procedure for calculation of monitor units for passively scattered proton radiotherapy beams. Med Phys. 2008;35:5088-5097. 30. Antonucci JV, Wallace M, Goldstein NS, et al. Differences in patterns of failure in patients treated with accelerated partial breast irradiation versus whole-breast irradiation: A matched-pair analysis with 10-year follow-up. Int J Radiat Oncol Biol Phys. 2009;74:447-452. 31. Vicini FA, Baglan KL, Kestin LL, et al. Accelerated treatment of breast cancer. J Clin Oncol. 2001;19:1993-2001. 32. Ye XP, Bao S, Guo LY, et al. Accelerated partial breast irradiation for breast cancer: A meta-analysis. Transl Oncol. 2013;6:619-627. 33. Polgar C, Fodor J, Major T, et al. Breast-conserving therapy with partial or whole breast irradiation: Ten-year results of the budapest randomized trial. Radiother Oncol. 2013;108:197-202.
www.practicalradonc.org
Original Report
Proton partial breast irradiation in the supine position: Treatment description and reproducibility of a multibeam technique Eric A. Strom MD a,⁎, Richard A. Amos MSc b, c , Simona F. Shaitelman MD a , Matthew D. Kerr BS b , Karen E. Hoffman MD a , Benjamin D. Smith MD a , Welela Tereffe MD a , Michael C. Stauder MD a , George H. Perkins MD a , Mayankumar D. Amin MSc a , Xiaochun Wang PhD b , Falk Poenisch PhD b , Valentina Ovalle MD a , Thomas A. Buchholz MD a , Gildy Babiera MD d , Wendy A. Woodward MD PhD a a
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas c Currently at Department of Radiotherapy Physics, University College London Hospitals NHS Foundation Trust, London, United Kingdom d Department of Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas b
Received 30 May 2014; revised 2 December 2014; accepted 29 January 2015
Abstract Purpose: Proton-accelerated partial breast irradiation (APBI) is early in its developmental phase without standardized treatment parameters. We report an approach to multibeam proton APBI using a universally available supine setup and deliberate beam arrangement strategy to limit the total area of skin receiving a full dose while being robust for interfraction variation. Methods and materials: Thirty-three American Society for Radiation Oncology consensussuitable/cautionary APBI candidates were treated using a passively scattered proton beam between 2010 and 2014 to 34 Gy relative biological effectiveness in 10 fractions twice daily. All patients were immobilized in a Vac-Lok cradle, typically with the arm down, and adducted to mound the breast and facilitate multiple, optimal en face beams. Radiopaque wires were placed on the surgical scar and 3 markers separate from the scar were placed elsewhere on the breast. All markers were used for each setup and removed before treatment. Marker displacement, wire rotation, and wire displacement were recorded from 10 random patients (100 orthogonal films). A 15-mm expansion was made to the tumor bed to obtain a clinical target volume, and followed by a 5-mm skin contraction and exclusion of the chest wall. A radial planning target volume margin of 5 mm was used.
Supplementary material for this article (http://dx.doi.org/10.1016/j.prro.2015.01.010) can be found at www.practicalradonc.org. Conflicts of interest: Dr Shaitelman reports grants from Elekta, outside the submitted work. Dr Smith reports grants from Varian Medical Systems, Inc, outside the submitted work. The rest of the authors have nothing to disclose. ⁎ Corresponding author. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Box 1202, Houston, TX 77030. E-mail address: [email protected] (E.A. Strom). http://dx.doi.org/10.1016/j.prro.2015.01.010 1879-8500/© 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.
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Results: Across 100 pretreatment images, median displacement of 3 distinct skin set-up markers was 3, 4, and 3 mm. Displacement of the scar wire in the X and Y direction was 0 and 1 mm, respectively. Among 28 verification scans performed, only 1 resulted in adaptive planning because of the initial presence of an air pocket in the lumpectomy cavity that resolved spontaneously during treatment. Conclusions: APBI proton treatment using a supine approach was largely reproducible. Inter-fraction variation demonstrates 5-mm radial planning margins were adequate; however, outliers do occur and films should be reviewed critically and in real time. This technique is straightforward and could be used at any proton facility without the need for specialized equipment. © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.
Introduction Breast conservation therapy using tumor excision followed by radiation is an established best practice for patients with early-stage breast cancer. 1-8 Recent experience has used a number of approaches to postexcision radiation therapy that deliver treatment only to the sector of the breast that was initially involved. These accelerated partial breast irradiation (APBI) techniques 9 include intracavitary radiation devices (brachytherapy), interstitial implants (also brachytherapy), intraoperative radiation techniques, and conformal linac-based external beam approaches. 10-16 With their unique dose-distribution features, protons for APBI are obvious tools to explore because they provide highly contained radiation with minimal dose outside the target region. Several institutions have reported initial clinical results of proton APBI. 17-19 A major drawback of protons is that passively scattered beams can have little or no skin sparing for superficial targets—delivering close to 100% of the prescribed dose to the skin for each beam. Indeed, the first clinical experience reported unexpected rates of skin toxicity using an approach in which only 1 field was treated per fraction. 20 Encouragingly, another group reported excellent cosmetic outcomes using a distinct multibeam technique, but in the prone position with a custom table. 21 We have previously reported a dosimetric exploration of a supine multibeam configuration that could deliver skin sparing with protons comparable to 3-dimensional conformal radiation therapy plans. 22 This study describes our initial experience with this proton APBI planning and treatment delivery technique and reproducibility using the supine approach.
Methods and materials Thirty-three American Society for Radiation Oncology consensus suitable/cautionary APBI candidates were treated between 2010 and 2014 using a passive scattered proton beam. The institutional review board approved this prospective protocol and all patients signed patientspecific consent before treatment. The protocol is registered with the National Cancer Institute as NCI2011-01102. To be eligible, patients were required to have
unifocal stage 0-I-II breast cancers ≤ 3 cm in size treated with lumpectomy. Surgically free margins were required and the target lumpectomy cavity must have been clearly delineated. Patients with multicentric carcinomas, 3 or more positive lymph nodes, nonepithelial breast malignancies, and those treated with initial chemotherapy were excluded.
Positioning All patients were immobilized supine in a Vac-Lok (Civco Medical Solutions) cradle, typically rotated slightly onto their contralateral side and with the ipsilateral arm down and adducted. Patients with very lateral tumor beds were treated with the arm abducted, still making every attempt to position the patient in such a way as to mound rather than stretch or flatten the breast. Optimally, proton beams are delivered perpendicularly to the skin surface so the tumor is at a consistent depth of tissue along the beam’s pathway. As in supplemental Fig 1A, tangential beams are susceptible to underdosing with relatively minor changes in positioning. 23 Further, with the arm down, it is easier to avoid clipping the anatomy on the scan field of view. Clipping creates image reconstruction artifacts throughout the computed tomography (CT) data (supplemental Fig 2), which has been shown to alter the proton range at the 50% distal isodose line by 2-3 mm; this is as much as a typical distal margin even when remote to the target. 24 In many cases, the arm and positioning can be used to mound the breast to create greater opportunity for en face arrangements (Fig 1). As in Fig 2, a radiopaque wire was placed on the surgical scar and markers were placed on the nipple and in at least 2 other locations on the breast separate from the scar to identify the breast contour. The wire displacement relative to the reference was measured 1 cm from the center of the wire in the X and Y directions for each anteroposterior film for each patient. Vector sums of X and Y displacements were recorded and the rotation calculated for each film. Further, the shortest displacement among the 3 markers including the nipple on the reference and image guided radiation therapy images was recorded for each film. All markers were used for orthogonal kV x-ray image guided setup before each treatment and were removed before proton beam delivery to avoid perturbation.
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Figure 1 Positioning. Sequential setup in the same patient illustrates the deliberate mounding of the breast with the arm down (A) versus the flattening of the upper inner quadrant (surgical bed) with the arm abducted (B).
Treatment planning was performed using Eclipse (Varian Medical Systems, Palo Alto, CA). The Hounsfield units of the radiopaque markers were overridden with air density for proton dose and range calculation. Marker displacement, wire rotation, and wire displacement at each treatment were recorded and assessed from 10 random patients (100 orthogonal films). Detailed setup information was presented for discussion as an e-poster at American Society for Radiation Oncology’s 2014 annual meeting. 25
Planning Target volume definitions and expansions are similar to those used in National Surgical Adjuvant Breast and Bowel Project B-39 for 3-dimensional conformal external beam APBI. However, because of the increased dose
conformality with protons, the volume of nontarget breast tissue treated is low 23,26,27 and constraints related to the portion of whole breast treated were never approached. The clinical target volume (CTV) was obtained initially by a 15-mm expansion on the tumor bed inclusive of clips and seroma. This volume was then contracted 5 mm from the skin and edited to exclude the chest wall, including the muscle. A radial planning target volume (PTV) margin of 5 mm was used. Proximal and distal beam-specific margins were 3.5% of the range + 1 mm from the CTV. Beam-specific range compensator smearing radii were calculated using 3% of the range and 5 mm positional uncertainty summated in quadrature. The prescribed dose was 34 Gy (relative biological effectiveness) in 10 fractions twice daily over a 1-week period, with a minimum 6-hour interfraction interval. Our goals for
Figure 2 Setup reproducibility. Ten anteroposterior image guided radiation therapy films from 10 randomly selected patients were reviewed for setup variability.
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dose constraints followed the guidelines of National Surgical Adjuvant Breast and Bowel Project B-39 and were met in all cases. Although not specifically required by the protocol, repeat CT scans were taken in the treatment position no later than the second fraction and were used to assess setup reproducibility and the effect of internal anatomical changes on the dose distribution. Thermoluminescent dosimeter measurements within the beam overlap on skin were obtained for the first 7 patients. Clinical evaluations were performed before and during radiation therapy, 2 and 6 weeks after completion of radiation therapy, and every 6 months thereafter. Acute and late toxicities were assessed using the Commom Terminology Criteria for Adverse Events criteria, version 4. 28
Statistics Descriptive statistics were generated using IBM SPSS Statistics, version 21.
Results All plans were free of CT artifacts related to clipping. Of 28 cases in which verification scans were performed (supplemental Fig 3), 1 treatment plan was adapted (supplemental Fig 3). This patient had an air pocket in the lumpectomy cavity at initial planning, which resolved spontaneously during treatment, altering the dose distribution. To expedite implementation of the adapted plan, field-defining apertures and range compensators were unchanged. To adapt the plan the range and spread-out Bragg peak of each beam was adjusted using the proton delivery system (Probeat, Hitachi America Limited, Inc, Tarrytown, NY). Monitor units were adjusted to account for the change in range shifter and spread-out Bragg peak factors. 29 Maximum thermoluminescent dosimeter dose ranged from 74% to 105% of the prescription (average, 97%). Median skin area included in all beams was 13 cm 2
Table 1
(standard deviation ± 11). The median portion of the heart receiving 5% of the prescription was 0%.
Reproducibility of treatment Setup variability summary statistics (across 100 measurements) are presented in Table 1. The summary statistics for individual patients are presented in Table 2. All values N 1 cm are highlighted in red. In general, the setup was adjusted to split the difference of any displacement across the multiple setup points, with more priority given to alignment of the scar wire because this closely associated with the tumor bed. Nonscar markers were generally permitted to have greater displacement. The radial PTV was 5 mm. Five patients (patients B, F, G, H, and I) had N 75% of measurements that were ≤ 5 mm for each displacement measurement (wire and markers). In 1 patient (E), the 75th percentile of 1 displacement measurement was N 5 mm. In 3 patients (patients A, C, and J), the 75th percentile of 2 displacement measurements were N 5 mm. The averages of these summary measurements per patient are presented in Table 3 to provide an overview across patients. Percentiles for individual patient data demonstrating variation N 1 cm are generally uncommon within 10 treatments. There was no discernable pattern among patients (initial cohorts vs later) or within-treatment fractions for any single patient (first half vs second half). Worst-case analysis was performed on the treatment plan for the patient with the largest setup displacement (patient A). This revealed that 34 Gy covered 96% of the CTV under this suboptimal circumstance. A graph of the robustness analysis performed for this patient is shown in supplemental Fig 4.
Discussion Adjuvant radiation therapy after breast-conserving surgery is a standard alternative for most patients with early-stage breast cancer that results in high success rates with infrequent complications. 5,6 The past decade has
Interpatient data summary (100 measurements across 10 patients) Rotation (°) Nipple marker (cm) Marker 2 (cm) Marker 3 (cm) Delta X (cm) Delta Y (cm) Vector XY (cm)
Mean Median Minimum Maximum Percentiles 25th 50th 75th
0.09 0.07 0.00 0.32 0.04 0.07 0.13
0.36 0.33 0.02 0.99 0.24 0.33 0.45
0.46 0.42 0.03 1.50 a 0.26 0.42 0.58
0.40 0.32 0.05 1.70 0.20 0.32 0.48
0.00 − 0.02 − 0.83 1.10 − 0.22 − 0.02 0.19
− 0.07 − 0.05 − 0.82 0.78 − 0.18 − 0.05 0.09
0.36 0.30 0.00 1.12 0.17 0.30 0.53
Rotation, delta X, delta Y, and vector XY refer to displacement of the wire placed on the lumpectomy scar taken 1 cm from the center of the wire. a Boldface type indicates values N 1 cm.
Practical Radiation Oncology: July-August 2015 Table 2 Patient A Mean Median Minimum Maximum Percentiles
Patient B Mean Median Minimum Maximum Percentiles
Patient C Mean Median Minimum Maximum Percentiles
Patient D Mean Median Minimum Maximum Percentiles
Patient E Mean Median Minimum Maximum Percentiles
Patient F Mean Median Minimum Maximum Percentiles
Patient G Mean Median Minimum Maximum Percentiles
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Intrapatient data summary Statistics
Rotation (°)
Nipple marker (cm)
Marker 2 (cm)
Marker 3 (cm)
Delta X (cm)
Delta Y (cm)
Vector XY (cm)
25th 50th 75th
0.09 0.08 0.00 0.23 0.04 0.08 0.14
0.54 0.51 0.30 0.89 0.41 0.51 0.65
0.45 0.48 0.20 0.75 0.29 0.48 0.54
0.77 0.63 0.30 1.70 a 0.47 0.63 1.06
0.15 − 0.02 − 0.40 1.10 − 0.11 − 0.02 0.45
0.03 − 0.02 − 0.17 0.26 − 0.08 − 0.02 0.19
0.36 0.24 0.09 1.12 0.14 0.24 0.48
25th 50th 75th
0.17 0.16 0.04 0.32 0.06 0.16 0.28
0.33 0.33 0.20 0.43 0.25 0.33 0.42
0.36 0.33 0.25 0.62 0.26 0.33 0.41
0.31 0.28 0.17 0.81 0.20 0.28 0.32
− 0.29 − 0.35 − 0.74 0.41 − 0.54 − 0.35 − 0.08
− 0.23 − 0.19 − 0.58 0.08 − 0.39 − 0.19 − 0.07
0.52 0.54 0.34 0.75 0.39 0.54 0.62
25th 50th 75th
0.05 0.04 0.01 0.10 0.03 0.04 0.07
0.52 0.50 0.10 0.99 0.22 0.50 0.87
0.53 0.44 0.03 1.50 0.31 0.44 0.67
0.45 0.43 0.12 1.15 0.27 0.43 0.51
0.12 0.13 − 0.30 0.64 − 0.23 0.13 0.35
− 0.19 − 0.18 − 0.58 0.08 − 0.30 − 0.18 − 0.11
0.36 0.31 0.11 0.86 0.21 0.31 0.44
25th 50th 75th
0.10 0.10 0.04 0.19 0.04 0.10 0.14
0.64 0.62 0.25 1.25 0.40 0.62 0.82
0.53 0.59 0.10 0.81 0.35 0.59 0.76
− 0.37 − 0.43 − 0.83 0.07 − 0.56 − 0.43 − 0.12
− 0.05 − 0.05 − 0.69 0.78 − 0.48 − 0.05 0.25
0.56 0.58 0.03 0.95 0.36 0.58 0.78
25th 50th 75th
0.03 0.03 0.00 0.05 0.02 0.03 0.04
0.25 0.24 0.13 0.37 0.15 0.24 0.36
0.84 0.84 0.26 1.37 0.49 0.84 1.24
0.34 0.30 0.12 0.93 0.15 0.30 0.45
0.33 0.26 0.07 0.69 0.15 0.26 0.52
0.04 0.03 − 0.14 0.24 − 0.04 0.03 0.13
0.36 0.29 0.13 0.70 0.18 0.29 0.52
25th 50th 75th
0.06 0.05 0.00 0.17 0.03 0.05 0.09
0.27 0.26 0.05 0.50 0.19 0.26 0.41
0.34 0.27 0.16 0.74 0.20 0.27 0.49
0.30 0.28 0.11 0.84 0.17 0.28 0.33
− 0.06 − 0.10 − 0.31 0.08 − 0.13 − 0.10 0.06
0.01 0.01 − 0.39 0.22 − 0.07 0.01 0.15
0.18 0.13 0.07 0.50 0.10 0.13 0.23
25th 50th 75th
0.13 0.12 0.06 0.23 0.09 0.12 0.17
0.41 0.45 0.20 0.63 0.29 0.45 0.49
0.32 0.36 0.07 0.53 0.20 0.36 0.44
0.36 0.33 0.09 0.84 0.23 0.33 0.46
− 0.11 − 0.14 − 0.27 0.12 − 0.25 − 0.14 0.02
− 0.16 − 0.15 − 0.39 0.02 − 0.24 − 0.15 − 0.06
0.23 0.24 0.02 0.47 0.12 0.24 0.31
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Table 2 (continued) Patient A Patient H Mean Median Minimum Maximum Percentiles
Patient I Mean Median Minimum Maximum Percentiles
Patient J Mean Median Minimum Maximum Percentiles
Statistics
Rotation (°)
Nipple marker (cm)
Marker 2 (cm)
Marker 3 (cm)
Delta X (cm)
Delta Y (cm)
Vector XY (cm)
25th 50th 75th
0.06 0.04 0.00 0.16 0.02 0.04 0.09
0.30 0.31 0.11 0.61 0.15 0.31 0.36
0.26 0.26 0.07 0.70 0.11 0.26 0.32
0.23 0.24 0.06 0.36 0.16 0.24 0.31
0.10 0.10 − 0.25 0.71 − 0.15 0.10 0.24
0.07 0.12 − 0.36 0.56 − 0.15 0.12 0.22
0.32 0.29 0.00 0.72 0.22 0.29 0.41
25th 50th 75th
0.07 0.07 0.00 0.19 0.02 0.07 0.11
0.35 0.35 0.17 0.51 0.28 0.35 0.42
0.38 0.39 0.23 0.60 0.29 0.39 0.47
0.29 0.27 0.05 0.69 0.15 0.27 0.41
0.09 0.03 − 0.33 0.59 − 0.11 0.03 0.35
0.02 0.04 − 0.47 0.51 − 0.13 0.04 0.17
0.32 0.29 0.07 0.75 0.12 0.29 0.45
25th 50th 75th
0.11 0.08 0.03 0.23 0.05 0.08 0.18
0.22 0.24 0.02 0.37 0.12 0.24 0.33
0.51 0.50 0.22 0.75 0.45 0.50 0.61
0.32 0.32 0.22 0.42 0.22 0.32
0.03 − 0.06 -0.22 0.40 − 0.12 − 0.06 0.21
− 0.26 − 0.23 − 0.82 0.23 − 0.56 − 0.23 0.00
0.39 0.32 0.10 0.85 0.19 0.32 0.58
Rotation, delta X, delta Y, and vector XY refer to displacement of the wire placed on the lumpectomy scar taken 1 cm from the center of the wire. a Boldface type indicates values N 1 cm.
shown the widespread introduction of several alternatives to classic whole breast irradiation, including several forms of APBI. A growing body of experience demonstrates that APBI may be comparable to whole breast irradiation in properly selected low-risk stage I-II breast cancer patients. 16,30-33 Several methods to deliver APBI are available, including intracavitary and interstitial brachytherapy, linacbased external beam radiation therapy, intraoperative radiation, and, most recently, proton beam therapy. Three centers have reported their initial clinical experiences with proton APBI. The first, from the Massachusetts General Hospital, involved 19 patients with stage I breast cancer treated to 32 Gy (relative biological effectiveness) in 8 fractions on a twice-daily schedule. 20 One to 3 fields were used for the plan, but only 1 field was treated per fraction. They reported high toxicity rates and noted several treatment planning issues that may
Table 3 Patient A
have contributed to these results recommending planning modifications for future use. The second, by Chang at al 19 from the Korean National Cancer Center, details their experience with 30 patients. They also identified significant acute skin reactions seen in their first 15 patients who were treated with only a single proton beam. Modifying their approach to a multiple beam plan appeared to dramatically reduce these skin reactions. Bush et al from Loma Linda University Medical Center have published their technique for APBI with a custom prone table. 21,26 This approach also facilitates the use of multiple appositional beams by rounding the breast through prone positioning. They treated patients to 40 Gy (relative biological effectiveness) in 10 daily fractions over 2 weeks. A total of 100 patients were treated with minimal toxicity and 90% good-excellent cosmetic outcomes. Because of the limited distribution of their custom prone
Average of summary statistics across patients (ie, average of the summary statistics in Table 2) Rotation (°) Nipple marker (cm) Marker 2 (cm) Marker 3 (cm) Delta X (cm) Delta Y (cm) Vector XY (cm)
Median 0.08 Standard deviation 0.06 Maximum 0.19
0.32 0.14 0.53
0.45 0.22 0.88
0.37 0.23 0.86
0.22 0.19 0.63
0.18 0.16 0.51
0.32 0.21 0.77
Rotation, delta X, delta Y, and vector XY refer to displacement of the wire placed on the lumpectomy scar taken 1 cm from the center of the wire.
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table, the applicability of this setup and these results to other centers is unknown. A readily available (nonpatented) reproducible setup was desirable. All 3 clinical trials studying the clinical role of proton beam APBI have used similar target volumes. The margins used to create a CTV and a PTV are essentially very similar to those used for 3-dimensional conformal APBI with photons as defined by Radiation Therapy Oncology Group B-39. This arbitrary choice of expansion volumes makes comparison between these external beam techniques fairly straightforward, but is distinct from the approaches used for brachytherapy APBI. Setup precision with proton APBI is particularly important because a geographic miss can occur in both the radial and distal directions. Typical image guided radiation therapy techniques optimized for deeper body structures are not easily applied to the breast, and strategies used to guarantee treatment reproducibility have limited applicability to proton treatments. For this reason, a detailed description of a workable technique for proton APBI fills an important gap as this modality undergoes additional clinical exploration. This study describes our approach to supine proton APBI using multiple beams. The prescribed dose was chosen taking into consideration the previous doses used by other institutions and estimating an effective dose of 44 Gy for late tissue effects with an α/β of 3. None of our 33 patients treated have developed grade 3 skin reactions, suggesting that the skin dose issues identified in the prior
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MGH and National Cancer Institute–Korea reports have been overcome. Because both of these studies clearly identified these issues after treating 19 and 15 patients, respectively, careful positioning—often with the arm down—was used to optimize the apical mounding of the breast and increase the number of options for appositional beams. Also, it is our impression that using the largest available Vac-Lok cradle with deliberate support around the entire torso and particularly the ipsilateral arm and shoulder aids in the reproducibility of the setup. For most patients, a 5-mm radial margin appears adequate considering that some markers may be well outside the target volume, and an individual measurement N 5 mm may not represent a clinically significant displacement or imply that the target is displaced beyond the PTV. However, it is important to emphasize the relevance of rejecting outlier films, particularly regarding displacement of markers closely related to the target, and worst-case scenario analysis should be considered in any patient for whom the first 2 films suggest N 5-mm displacement in key markers. Proton APBI, although still in the exploratory phase, has a number of highly valued features. Dose to heart and lung can be practically eliminated and dose to rib and nontarget breast tissue can be quite low. Skin-sparing appears to be effectively achieved using multibeam approaches; however, these also introduce a greater degree of uncertainty with respect to CTV coverage. Robust treatment techniques are needed for proton APBI to fulfill
Figure 3 Cosmetic outcome examples. (Top) Cosmesis at completion of therapy, 5 weeks, 7 weeks, and 1 year in a patent with good cosmesis. Slight hyperpigmentation was evident in the field distribution at 1 year. (Bottom) Three examples of 1-year follow-up among patients with excellent cosmesis.
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its potential. This is the first detailed description of such a technique. Although the primary study endpoints cannot yet be completely assessed because accrual is still open, none of the toxicity monitoring thresholds has been crossed and no patients have developed grade 3 skin reactions (Fig 3). We describe a robust multibeam proton APBI technique that is straightforward and could be used at any proton facility without the need for specialized equipment.
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