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Strahlentherapie und Onkologie

Original Article

A Dosimetric Comparison of IORT Techniques in Limited-Stage Breast Cancer Olaf Nairz1, Heinz Deutschmann1, Michael Kopp1, Karl Wurstbauer1, Gerhard Kametriser1, Gerd Fastner1, Florian Merz1, Roland Reitsamer2, Christian Menzel2, Felix Sedlmayer1

Background and Purpose: For intraoperative radiotherapy (IORT) during breast-conserving treatment four different techniques have been addressed: interstitial brachytherapy, an inflatable balloon with a central high-dose-rate source (MammoSite), a miniature orthovolt system (Intrabeam), and linac-based electron radiotherapy (IOERT). The dosimetric properties of these methods are compared. Material and Methods: Planning target volumes (PTVs) of the same size but of different shapes are assumed, corresponding to the technique’s specific situs. Dose distributions for the PTVs and for surrounding tissues are demonstrated by dose-volume histograms and a list of physical parameters. A dose inhomogeneity index (DII) is introduced to describe the deviation of a delivered from the prescribed dose, reaching its minimal value 0 in case of perfect homogeneity. Results: In terms of DII, IOERT reaches the lowest value followed by the MammoSite, the Intrabeam and interstitial implants. The surrounding tissues receive the smallest average dose with IOERT, closely followed by the orthovolt system. Conclusion: When comparing simplified geometric figures, IOERT delivers the most homogeneous dose distributions. However, in clinical reality PTVs often present asymmetric shapes instead of ideal geometries. Due to a strictly centric dose fall-off, any system with a round central applicator will have technical limits. During IOERT margin-directed applicator guidance is possible and interstitial brachytherapy allows for polygonal dose shaping. These techniques seem to be superior for asymmetric PTV irradiation. Key Words: Breast cancer · Intraoperative radiotherapy · IORT · PTV · Dosimetry Strahlenther Onkol 2006;182:342–8 DOI 10.1007/s00066-006-1580-2 Dosimetrischer Vergleich von IORT-Techniken beim konservativ operierten Mammakarzinom Hintergrund und Ziel: Für die intraoperative Radiotherapie (IORT) des konservativ operierten Mammakarzinoms sind vier Techniken in Gebrauch: die interstitielle Brachytherapie, ein aufblasbarer Ballon mit einer zentralen High-Dose-Rate-Quelle (MammoSite), ein Miniatur-Orthovoltsystem (Intrabeam) sowie Elektronen am Linac (IOERT). Die dosimetrischen Eigenschaften dieser Methoden werden verglichen. Material und Methodik: Für jede dieser Techniken werden Planungszielvolumina (PTVs) des gleichen Volumens, aber unterschiedlicher Form angenommen, die dem jeweiligen typischen Situs zum Zeitpunkt der Applikation entsprechen (Abbildung 1, Tabellen 1 und 2). Die Dosisverteilungen (Abbildung 2) inner- und außerhalb der PTVs werden mittels Dosis-Volumen-Histogrammen und einer Reihe von Parametern miteinander verglichen (Abbildung 3, Tabelle 3). Ein Dosisinhomogenitätsindex (DII) wird vorgestellt, der die Abweichung einer verabreichten von einer vorgeschriebenen Dosis beschreibt und im Fall einer perfekten Homogenität den Minimalwert 0 erreicht. Ergebnisse: In Bezug auf den DII erreicht die IOERT den niedrigsten Wert, gefolgt von MammoSite, dem Orthovoltsystem und den interstitiellen Implantaten. Das umgebende Gewebe erhält die geringste mittlere Dosis mittels IOERT, knapp gefolgt vom Intrabeam (Abbildung 3, Tabelle 3). Schlussfolgerung: Die IOERT zeigt die homogenste Dosisverteilung. In der klinischen Realität weisen PTVs aber häufig asymmetrische anstelle idealgeometrischer Formen auf. Durch den strikten zentralen Dosisabfall bestehen bei Systemen mit runden zentralen Applikatoren technische Limitationen. Während einer IOERT ist eine asymmetrische Applikatorführung möglich, die interstitielle Brachytherapie erlaubt eine polygonale Dosisformung, weshalb diese beiden Verfahren zur Erfassung asymmetrischer PTVs überlegen scheinen (Abbildung 4). Schlüsselwörter: Mammakarzinom · Intraoperative Radiotherapie · IORT · PTV · Dosimetrie 1 2

Department of Radio-Oncology, Salzburger Landeskliniken and Paracelsus Private Medical University (PMU), Salzburg, Austria, Department of Special Gynecology, Salzburger Landeskliniken and Paracelsus Private Medical University (PMU), Salzburg, Austria.

Received: March 15, 2006; accepted: March 20, 2006

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Strahlenther Onkol 2006 · No. 6 © Urban & Vogel

Nairz O, et al. IORT Techniques for Breast Cancer

Introduction Intraoperative radiotherapy (IORT) to the tumor bed during breast-conserving surgery has become a booming field of interest for partial-breast irradiation, either as anticipated boost or as sole treatment in limited-stage breast cancer [24, 25]. The aim of breast IORT is an utmost precise dose delivery to the area at highest risk for contamination with subclinical tumor cells [1, 6, 7, 12, 27, 31]. This has given rise to the development of different technical approaches, with the term “IORT” used for the following techniques: perioperative multicatheter brachytherapy, endocavitary brachytherapy, an orthovolt system, and intraoperative radiotherapy with electrons on linear accelerators (IOERT). Perioperative multicatheter brachytherapy corresponds to classic interstitial brachytherapy by flexible needles, applied during open sight of the excision hole [14, 19–21, 28, 33]. Endocavitary IORT, the so-called MammoSite, is performed by an inflatable balloon which is placed into the lumpectomy cavity and filled with sterile saline to a size that fills the cavity completely, typically 4 cm in diameter. A high-dose-rate source is guided into the balloon’s center with the dose normally prescribed 1 cm from the surface of the balloon [5, 9, 13]. For both brachytherapy techniques only the applicators’ positionings are true intraoperative maneuvers, with the irradiation being performed postoperatively, thus allowing for fractionated treatments. In contrast to these brachytherapy techniques, IOERT and orthovolt treatments are IORTs sensu stricto. The orthovolt system (Intrabeam) consists of a miniature electron-driven low-energy X-ray source, emitting an isotropic X-ray spectrum. For breast irradiations spheric applicators, chosen according to the excision cavity’s size, are put at the top of the source, resulting in a similar configuration as for the MammoSite system: a point source at the center within a spheric applicator [15, 29, 30]. Finally, IOERT is possible with various electron energies, with the walls of the excision hole temporarily approximated by central sutures to bring the target volume into reach for the electron beam, which is applied by round tubes of different diameters [2, 4, 8, 16, 18, 19, 22, 26, 32]. The aim of our study was to investigate the dose distributions of these four techniques for identical clinical preconditions and the analysis of their dosimetric properties. One parameter quantifying the homogeneity of the dose distribution with a simple and intuitive interpretation will be defined and discussed. Material and Methods Planning Target Volume (PTV) and Surrounding Tissue Shapes The PTV size was generally assumed with roughly 80 ml, which is in accordance with frequently reported treatment volumes [10]. For all IORT techniques typical PTV shapes were created which correspond to their specific surgical situs at the time of the IORT maneuver (Figure 1).


In case of the MammoSite and the Intrabeam system, the PTV is treated by a round central applicator and therefore supposed to be a shell around its surface. For both techniques we assumed an applicator’s diameter of 4 cm and a shell thickness of 1 cm. In case of perioperative brachytherapy three different shapes were allowed to study the possible influence of central seromas of various sizes: the first assumption was a spherical shell of 1 cm thickness with a 4-cm seroma, resulting in the identical PTV shape as for the MammoSite and the Intrabeam. Furthermore, we calculated for two oblate spheroids, one without and one with an elliptical seroma inside. By contrast, IOERT will have to encompass PTV shapes which have rather the shape of half prolate spheroids according to the surgical preparation technique. Table 1 gives a summary of the shapes and dimensions of the target volumes for the different IORT techniques. For dosimetric comparisons not only PTVs but also the surrounding tissues were considered. They were assumed to have a volume of roughly 400 ml for all cases. Their shapes and dimensions are summarized in Table 2. Dose Calculation The dose distribution for interstitial brachytherapy and the MammoSite system was calculated by assuming 192Ir point sources and the dose to be applied to water. In this approximation the dose at a distance r from the source is given by D(r)∝

g(r)

(equation 1) with g(r) the water perturbation correction, which was approximated by a fourth-order polynomial [17]. r2

ST PTV Applicator/ seroma

a

ST PTV Seroma

b ST

PTV

ST PTV

c

d

Figures 1a to 1d. Idealized shapes for the target volumes and surrounding tissues for the different techniques of intraoperative irradiation. Dimensions given in Tables 1 and 2. a) MammoSite, Intrabeam and brachytherapy five-layer; b) brachytherapy three-layer; c) brachytherapy two-layer; d) IOERT. Abbildungen 1a bis 1d. Idealisierte Geometrien für die Planungszielvolumina und das umgebende Gewebe für die verschiedenen intraoperativen Bestrahlungstechniken. Abmessungen s. Tabellen 1 und 2. a) MammoSite, Intrabeam und fünflagiges Brachyimplantat; b) dreilagiges Brachyimplantat; c) zweilagiges Brachyimplantat; d) IOERT.

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Table 1. Dimensions of the planning target volumes (PTV) for the IORT techniques. IOERT: intraoperative electron radiotherapy; NA: not applicable. Tabelle 1. Abmessungen der Zielvolumina (PTV) für die verschiedenen intraoperativen Bestrahlungstechniken. IOERT: intraoperative Radiotherapie mit Elektronen; NA: nicht anwendbar. IORT technique

PTV shape

PTV inner dimensions (cm) Semimajor axis Semiminor axis

PTV outer dimensions (cm) Semimajor axis Semiminor axis

PTV volume (ml)

MammoSite Intrabeam Brachy five-layer Brachy three-layer Brachy two-layer IOERT

Spherical shell Spherical shell Spherical shell Oblate spheroid shell Oblate spheroid Half prolate spheroid

2 2 2 1.5 NA NA

3 3 3 3.2 4.0 4.2

79.6 79.6 79.6 80.7 80.4 79.2

2 2 2 1.0 NA NA

3 3 3 2.1 1.2 3.0

Table 2. Dimensions of the surrounding tissues (ST) for the different techniques (rounded to one digit). IOERT: intraoperative electron radiotherapy. Tabelle 2. Abmessungen des umgebenden Gewebes (ST) für die verschiedenen Bestrahlungstechniken (auf eine Kommastelle gerundet). IOERT: intraoperative Radiotherapie mit Elektronen. IORT technique

ST shape

ST inner dimensions (cm) Semimajor axis Semiminor axis

ST outer dimensions (cm) Semimajor axis Semiminor axis

ST volume (ml)

MammoSite Intrabeam Brachy five-layer Brachy three-layer Brachy two-layer IOERT

Spherical shell Spherical shell Spherical shell Oblate spheroid shell Oblate spheroid shell Half prolate spheroid shell

3 3 3 3.2 4.0 4.2

5.0 5.0 5.0 5.6 7.3 7.6

401 401 401 400 401 402

For interstitial brachytherapy, we designed five-, threeand two-layer implants with 14, 9 and 13 needles, respectively, in order to achieve best coverage of the three target volumes. The needles were arranged to form equilateral triangles with a side length of 1.5 cm. The step size of the source inside the applicators was assumed to be 2.5 mm. All source positions were equally weighted and only positions inside the borders of the PTV were loaded. In order to exclude infinite contributions to the dose matrix, the radius of the needles and thus the minimum distance between source and tissue was assumed to be 1 mm. In that way we avoided unphysical dose peaks and the quotation of the maximum dose value for interstitial brachytherapy becomes more meaningful. The dose distribution matrix of the MammoSite system resulted from a single point source at the center of the balloon. The balloon was assumed to be filled with water yielding a homogeneous transition to the surrounding tissues. The maximum dose is applied to the tissue at the applicator’s surface. For the orthovolt system a dose fall-off obeying a 1/r3-law was reported in the literature [3] – with r the distance from the target at the tip of the drift tube – but for the case that no applicator is used. An applicator modifies the dose distribution and a correction term of the general form exp(a + b · r 0.5 + c · r –1.5) has to be multiplied to the 1/r3-term, the parameters a, b and c depending on the applicator’s diameter [11]. Since, to our

344

3 3 3 2.1 1.2 3.0

5.0 5.0 5.0 3.7 2.2 5.5

knowledge, no data exist in the literature for the case of a 4-cm applicator, we derived these parameters from the data reported for a 3.5-cm applicator [29], assuming that these parameters will be the same for a 4-cm applicator. Investigations by Herskind et al. [11] suggest that no significant quantitative error may be introduced by this procedure. The correction to the 1/r3-fall-off was lower than 10% for both the PTV and the surrounding tissue. For IOERT the dose distribution matrix was derived from an actually measured dose applied to water by a linear accelerator (Elekta SL 18). For our study situation we assumed that the surgeon prepared the tissue to be irradiated in a shape of half of a prolate spheroid with a diameter of 6 cm and a depth of 4.2 cm. The best coverage for that situation was achieved by taking a tube of 7 cm in diameter and 25 cm in length, which corresponds to a focus-surface distance of 118 cm, and the tissue irradiated by energies of 12 and 15 MeV weighted in a relation of 1 : 2.2. Dose Comparison The dose matrices of all these six situations were multiplied with a factor so that the points of the minimum dose inside the target volumes got the value of 90. This value is interpreted as the percentage of the reference dose and fixed as the minimum dose required. So the comparison of dose distributions of different techniques regardless of absolute dose deliveries becomes possible.



For each technique we specified several prominent parameters both for the PTV and the surrounding tissues as the minimum, the maximum, the mean, the median dose, and the volume-related doses D90 and D10. D90 (D10) is obtained when from all dose matrix elements of the considered volume that subset is taken, which represents 90% (10%) of the volume and contains the highest values. From this subset the smallest value is picked. Furthermore, we tried to summarize the main characteristics of the dose distribution in one single parameter, which will be called dose inhomogeneity index (DII). It is defined as the mean deviation of the dose inside the PTV from the prescribed dose

Dp,Vx, y, z

V

dVx, y, z

(equation 2)

or in its discrete form n

Σ

i=1

DII =

Da,Vi – Dp,Vi Dp,Vi n

Σ Vi

·Vi

Vi = const.

=

1 n

n

Da,Vi – Dp,Vi

i=1

Dp,Vi

Σ

(equation 3)

i=1

Results A visualization of the dose distributions is given in the two-dimensional plots in Figure 2. In Figure 3 the dose-volume histograms (DVHs) of the target volumes and the surrounding tissues are shown. It is evident that for IOERT the steepest DVH is achieved, whereas the


Dose distribution orthovolt

Dose (% of reference dose)

Dose distribution MammoSite 200 150 100 50 0 2 y-axis

0 −2

−2

0

2 x-axis

a

300 200 100 0 2 y-axis

c

0 −2

−2

0

2 x-axis

b Dose distribution brachytherapy 5-layer


where Da,V and Dp,V are the actual and prescribed dose in the corresponding voxel, respectively, Vi the size of the voxel, and n the number of voxels of the considered volume. In the most common case that all voxels have the same size, the absolute values of the deviations per voxel dose are added and divided by the number of voxels. Taking the absolute value guarantees that no compensation of underdosage by an overdosage in another region is possible. In the ideal case of a completely homogeneous irradiation, where the whole PTV receives the prescribed dose, the DII becomes 0. It becomes larger with growing dose inhomogeneity. The DII multiplied with 100 gives the mean absolute deviation from the prescribed dose in the PTV in percent.

Discussion and Conclusion When comparing tele- with brachytherapeutic maneuvers for IORT, it is possibly misleading to consider single isolated


Da,Vx, y, z – Dp,Vx, y, z

1 V

300 200 100 0 2 y-axis

0 −2

−2

0

2 x-axis

Dose distribution IOERT Dose (% of reference dose)

DII =

dose spread is highest for the two-layer implant. For the surrounding tissues the DVHs show that the minimum dose is lowest for IOERT, whereas the high-dose region has the smallest volume using Intrabeam. A summary of all above-mentioned parameters is given in Table 3. With respect to the PTV, IOERT delivers the most homogeneous dose distribution, being free from any dose peaks which are most pronounced in interstitial brachytherapy and the orthovolt system. In terms of DII, IOERT reaches a value of 0.047, followed with a clear gap by the MammoSite system (0.295), orthovolt treatment (0.505), and the interstitial implants (0.648–1.581). Furthermore, IOERT has an average dose inside the target volume closest to the prescribed dose and the smallest maximum dose. The surrounding tissues receive the highest doses with the interstitial implants and, together with the MammoSite system, also the highest minimum dose. The minimum dose is lowest with IOERT and also the average dose is smallest with this technique, closely followed by the Intrabeam system.

100 50 0 2 y-axis

0 −2

−2

0

2 x-axis

d

Figures 2a to 2d. Dose distribution in the equatorial plane of the MammoSite system (a), the Intrabeam system (b), and interstitial brachytherapy for the case of spheric seroma (c). The graph for IOERT (d) shows the dose distribution in a plane containing the beam central axis. The dose inside the applicator for the Intrabeam system and inside the balloon for the MammoSite system was set to 0. Abbildungen 2a bis 2d. Dosisverteilung in der Äquatorialebene beim MammoSite-System (a), beim Intrabeam-System (b) und bei der fünflagigen interstitiellen Brachytherapie mit kugelförmigem Serom (c). Der Graph für die IOERT (d) zeigt die Dosisverteilung in einer den Zentralstrahl enthaltenden Ebene. Die Dosis innerhalb des Applikators beim Intrabeam- und MammoSite-System wurde auf 0 gesetzt.

345


of dose homogeneity within the PTV and at the same time sparing surrounding tissues also the best. However, before overemphasizing the role of physical dose homogeneity, the dignity of IORT maneuvers has also to be judged with respect to intraoperative clinical reality, which might differ enormously from ideal geometric conditions. A discussion about advantages and pitfalls of 0 50 100 150 200 250 300 350 0 10 20 30 40 50 60 70 80 90 100 IORT techniques has to consider their a Dose (%) b Dose (%) adaptability to an individual surgical siFigures 3a and 3b. Dose-volume histograms for the target volume (a) and the surrounding tus where asymmetric instead of symtissue (b). metric PTVs have to be encompassed. Abbildungen 3a und 3b. Dosis-Volumen-Histogramme für das Zielvolumen (a) und das umgeNeither does tumor spread follow strictbende Gewebe (b). ly equidistant concentric growth, nor will the surgeon be able to perform a tunumbers. Therefore, we introduced a single parameter, the mor removal which is perfectly equidistant in all directions in DII, to characterize the dosimetric dignity of the implant. It is terms of normal-tissue margins (Figure 4). The shape of a reimportant to note that the DII is not merely a measure of the maining PTV which is assumed to be subclinically contamispread of the values of the dose matrix but is also a measure nated with tumor cells resembles a “sickle room” rather than of the deviation of the dose values from the prescribed dose. a shell, demanding for asymmetric spatial dose delivery. Due This distinguishes the DII from the standard deviation: the to a strictly centric dose fall-off, any system with a round censtandard deviation is a measure of the deviation from the avtral applicator will have technical limits which cannot always erage dose, but the average dose is in general different from be compensated by surgical preparation techniques. During the prescribed dose. IOERT, excentric applicator guidance is possible. However, With respect to typical and idealized geometric PTV the histopathologic information about the extent of free marshapes, the physical dose comparison clearly revealed IOERT gins has to be provided during the operation, emphasizing the to be by far best suited of all IORT techniques, both in terms role of telepathology in this setting. In situ components will Volume (%)

MammoSite Orthovolt Brachy 5-layer Brachy 2-layer Brachy 3-layer IOERT

100 90 80 70 60 50 40 30 20 10 0

MammoSite Orthovolt Brachy 5-layer Brachy 2-layer Brachy 3-layer IOERT

Volume (%)

100 90 80 70 60 50 40 30 20 10 0

Table 3. Summary of the most important statistical parameters characterizing the dose distributions inside the target volumes (PTV) and the surrounding tissues (ST). Dmin: minimal dose in the considered volume (was set to 90% for all cases); Dmax: maximal dose in the considered volume; D90: minimal dose to 90% of the considered volume which receives the highest doses; D10: minimal dose to 10% of the considered volume which receives the highest doses; Dav: average dose; Dmedian: median dose; DII: dose inhomogeneity index (average absolute value of deviation from prescribed dose); IOERT: intraoperative electron radiotherapy. Tabelle 3. Zusammenfassung der wichtigsten statistischen Parameter, die die Dosisverteilung im Zielvolumen (PTV) und im umgebenden Gewebe (ST) charakterisieren. Dmin: Minimaldosis im betrachteten Volumen (wurde für alle betrachteten Fälle auf 90% gesetzt); Dmax: Maximaldosis im betrachteten Volumen; D90: Minimaldosis für den Teil des Volumens, der die höchste Dosis erhält und 90% des gesamten Volumens umfasst; D10: Minimaldosis für den Teil des Volumens, der die höchste Dosis erhält und 10% des gesamten Volumens umfasst; Dav: durchschnittliche Dosis; Dmedian: mediane Dosis; DII: Dosisinhomogenitätsindex (durchschnittliche absolute Abweichung von der vorgeschriebenen Dosis); IOERT: intraoperative Radiotherapie mit Elektronen.

PTV

ST

346

Dmin Dmax D90 D10 Dav Dmedian DII Dmin Dmax D90 D10 Dav Dmedian

MammoSite

Intrabeam

Brachy five-layer

Brachy three-layer

Brachy two-layer

IOERT

90 200 94 174 127 120 0.295 33 90 35 74 50 46

90 276 96 228 149 135 0.505 22 90 24 68 40 35

90 635 111 226 165 150 0.648 33 486 37 90 58 51

90 709 122 262 189 173 0.893 22 852 28 142 71 53

90 969 136 371 258 243 1.581 25 540 30 89 55 47

90 110 100 109 104 105 0.047 4 102 6 85 37 28



Figures 4a to 4d. Typical surgical situs and its influence on IORT maneuvers. Green lines: coverage by reference dose. a) Non-equidistant surgical removal of the tumor leaves asymmetric PTV shapes (“sickle rooms”). b) Round central applicators are at risk of leaving tumor cells out of reach. c) With IOERT margin-directed applicator guidance is possible. d) Interstitial brachytherapy allows for polygonal dose shaping. Abbildungen 4a bis 4d. Typischer chirurgischer Situs und sein Einfluss auf das IORT-Manöver. Grüne Linien: Abdeckung mit Referenzdosis. a) Nicht-äquidistantes chirurgisches Entfernen des Tumors hinterlässt asymmetrische Zielvolumina („Sichelraum“). b) Bei kugelförmigen Applikatoren besteht dabei die Gefahr, dass Tumorzellen nicht erreicht werden. c) Resektionsrand und durch den Applikator festgesetztes Zielvolumen können bei IOERT in Deckung gebracht werden. d) Polygonale Dosisformung ist bei interstitieller Brachytherapie möglich.

not be judgable by frozen sections only, which may lead to discrepancies with the final histological assessments. In our own early series, up to 10% of the patients were referred to reexcisions and/or secondary mastectomies [22, 23, 26]. Perioperative interstitial brachytherapy has the advantage that definitive histopathologic information might already be available at the beginning of treatment, allowing also for asymmetric spatial dose shaping.

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Address for Correspondence Dr. Olaf Nairz Salzburger Landeskliniken und Paracelsus Medizinische Universität (PMU) Muellner Hauptstraße 48 5020 Salzburg Austria Phone (+43/662) 4482-3949, Fax -3903 e-mail: [email protected]
