Multisource Rotating Shield Brachytherapy Apparatus for Prostate Cancer (2024)

Abstract

Purpose

To present a novel multisource rotating shield brachytherapy (RSBT) apparatusfor the simultaneous precise angular and linear positioning of partially-shielded¹⁵³Gd brachytherapy sources in interstitial needles for the treatment oflocally-advanced prostate cancer. It is designed to lower the dose to nearby healthytissues, the urethra in particular, relative to conventional high-dose-ratebrachytherapy (HDR-BT) techniques.

Methods and Materials

Following needle implantation through the patient template, an angular drivemechanism is docked to the patient template. Each needle is coupled to a multisourceafterloader catheter by a connector passing through a shaft. The shafts are rotatedabout their axes by translating a moving template between two stationary templates.Shafts’ surfaces and moving template holes are helically threaded with the samepattern such that translation of the moving template causes simultaneous rotation of theshafts. The rotation of each shaft is mechanically transmitted to thecatheter/source/shield combination, inside the needles, via several key/keyway pairs.The catheter angles are simultaneously incremented throughout treatment, and only asingle 360° rotation of all catheters is needed for a full treatment. For eachrotation angle, source depth in each needle is controlled by a multisource afterloader,which is proposed as an array of belt-driven linear actuators, each of which drives awire that controls catheter depth in a needle.

Results

Treatment plans demonstrated RSBT with the proposed apparatus reduced urethralD_0.1cc below that of conventional HDR-BT by 31%for urethral dose gradient volume within 3 mm of the urethra surface. Treatment time todeliver 20 Gy with the proposed multisource RSBT apparatus using nineteen 62.4 GBq¹⁵³Gd sources is 122 min.

Conclusions

The proposed RSBT delivery apparatus enables a mechanically feasibleurethra-sparing treatment technique for prostate cancer in a clinically reasonabletimeframe.

1. INTRODUCTION

High-dose-rate brachytherapy (HDR-BT) for prostate cancer is an effective prostatecancer therapy that can be delivered as a monotherapy (Demanes et al 2014)^1–6or a boost to external beam radiotherapy.^7–16 While achieving tumorcontrol is paramount, prostate cancer patients may live with the side effects of theirtreatment for decades, and anticipated side effects play a strong role in treatmentdecisions.^17,18 Urinary retention and urethral stricture have been shown to beexperienced at higher rates by patients undergoing BT monotherapy or EBRT with HDR-BT boostthan by patients undergoing EBRT alone.^19,20 Urethral stricture, occurring mostly in thebulbomembranous urethra or apex/external sphincter region,²¹ is the most frequent late toxicity of combined EBRT andHDR-BT treatments.²² The reported urethralstricture rates (5.2%,²³6.6%,²⁴ 8%,²² and 10%²⁰) are considerably greater than those reported for EBRTmonotherapy (1.7%,²³2%,²⁰ and 3%^25,26).Urethral brachytherapy dose is likely the underlying cause of urethral stricture in combinedEBRT and HDR-BT treatments.^27–29

The target conformity and bladder, urethra, and rectal sparing capabilities ofconventional HDR-BT is restricted based on the geometric constraints imposed by the positionand shape of the catheters, as well as the radially symmetric radiation dose distributionsemitted by conventional unshielded BT sources. Dose distribution conformity and sensitivehealthy tissue avoidance can be considerably improved through the use of rotating shieldbrachytherapy (RSBT) in conjunction with a ¹⁵³Gd radiation source that isamenable to partial shielding within an interstitial needle (¹⁹²Ir isnot).^30–33 The sources rotate during delivery in an optimizedfashion,^34,35 directing dose away from sensitive structures and into the targetedtissue.

The purpose of the current work is to introduce a novel, multisource, prostate RSBTapparatus. In a previous study,³¹ apartially-shielded source/catheter/needle system was defined, based on the ¹⁵³Gdisotope, and was shown by simulation to be capable of lowering the urethral dose up to44% relative to conventional HDR-BT. An apparatus for mechanically delivering thedose through the inserted needles was not proposed, however, and the multisource RSBTapparatus presented here overcomes the technical barriers to implementation of thepreviously proposed approach.³¹ Since thedose rate per unit mass for ¹⁵³Gd is substantially lower than that of¹⁹²Ir, multiple shielded ¹⁵³Gd sources need to be usedsimultaneously in order to deliver RSBT dose distributions of up to 20 Gy in a clinicallyacceptable time of fewer than 2 hours. The apparatus presented in this work can control theemission angles and depths of up to 20 partially-shielded ¹⁵³Gd sourcessimultaneously.

2. METHODS AND MATERIALS

2.A. Brachytherapy source

Enabling the multisource RSBT technique requires an appropriate radioisotope anda technically feasible rotating shield system that fits inside a 14-gauge needle used forprostate cancer brachytherapy. For this apparatus ¹⁵³Gd is selected as thesource isotope due to its reasonable dose rate, energy spectrum ranging from 40 keV to 105keV (60.9 keV average), half-life of 242 days, and its potential for mass production vianeutron irradiation of ¹⁵¹Eu or ¹⁵²Gd.³¹ A nitinol (NiTi) RSBT needle containing a rotatingcatheter as well as a shielded ¹⁵³Gd source was designed, and the dose ratedistribution about the partially shielded source was calculated using the MCNP5 MonteCarlo code and a published ¹⁵³Gd spectrum,³⁶ with photons emitted in the intermediate range of 40–105 keV.The modeled source was a 7.41 g/cm³ Gd₂O₃ pelletcontaining 2,442 GBq of ¹⁵³Gd per gram of Gd₂O₃, whichcould be generated by neutron irradiation of spent dual-photon absorptiometry sourcescontaining about 87% ¹⁵²Gd.³⁷ The Monte Carlo dose calculation method is the same as that employedby.³¹

The shielded ¹⁵³Gd source and its calculated relative dose ratedistribution are shown in Figure 1(a) and 1(b), respectively. The source exhibits azimuthalanisotropy in its dose rate distribution due to the presence of platinum shielding on oneside. In the proximal and distal directions, the platinum shield shown in Figure 1(a) has cylindrical platinum end cap welded to it thatprevent the ¹⁵³Gd source pellet from sliding out. The end caps function asreceivers for the aluminum window, and, when they are welded to the platinum shield, thealuminum window is fixed in place. The dose rate on the platinum shielded side of thesource at 1 cm off-axis was to about 7% of that on the unshielded side. Thecalculated dose rate of the RSBT source 1 cm from the geometric center of the catheter onthe side with the aluminum window and along the axial plane passing through the geometriccenter of the active radiation source was 6.82×10² cGyh⁻¹. The dose rate at 1 cm from the central axis of the¹⁹²Ir source was 4.246×10⁴ cGy h⁻¹along the axial plane passing through the geometric center of the active source.

Multisource Rotating Shield Brachytherapy Apparatus for Prostate Cancer (1)

2.B. Multisource angular drive mechanism

The RSBT system is equipped with an angular drive mechanism that controls therotation of nitinol catheter-mounted source/shields for all implanted needlessimultaneously. Following needle implantation, the angular drive mechanism is docked tothe patient template in which the needles are all held at the same rotation angle at agiven time while the catheters are rotated by translating a moving template between twostationary templates using redundant motors. A two-frame conceptual diagram of the angulardrive mechanism is shown in Figure 2. It consists ofthe cross section of five points along a single inserted needle starting from thecombination of the afterloader wire and the connector to the combination ofneedle/source/shield inside the prostate. Figure 2shows how translational motion of the moving template causes a 180° rotation of ashielded source inside a needle. When the moving template is translated longitudinally theshafts rotate, as threaded holes of the moving template exert enough resistive force tothe threaded exterior peripheral wall of the shaft which is fixed axially. The angularorientation of the shielded source is also fixed and known during treatment via a proximalkeyed cuff that attaches the remote afterloader wire to the source catheter. Partialshields around the sources are oriented at a known angle by means of the keys and thekeyways machined into various parts.

Multisource Rotating Shield Brachytherapy Apparatus for Prostate Cancer (2)

Figure 3 shows the whole multichannelangular drive mechanism with all the shafts and templates, which is docked to twentyinserted needles. As shown, the connector can move freely in the longitudinal direction inorder to connect with needles that protrude from the patient at varying distances. Therotating shafts are threaded to provide a pitch with 10 cm translation per shaft rotation(1 mm per 3.6° rotation), which is sufficient to balance the tradeoffs betweenrotational accuracy, apparatus length, and resistive force exerted on the moving templateby the shafts during motion. In order to create the desired translation of the movingtemplate, four motors are arranged to rotate the lead screws contacting the movingtemplate. When the lead screws rotate, the moving template translates longitudinally whilethe other two templates provide rigidity to the system.

Multisource Rotating Shield Brachytherapy Apparatus for Prostate Cancer (3)

2.C. Multisource remote afterloader

The depth positions of the radiation sources are determined via a remoteafterloader (Figure 4) consisting of twentyParker-Hannifin^® (PH) (Parker, Rohnert Park, CA, USA) 1,000-mm travelbelt-driven linear actuators that have 0.2 mm positional reproducibility and are assembledin the vertical orientation. A 1.8-mm-diameter 7×7 flexible stainless steelbraided wire is attached to the carriage (yellow) of each actuator and moved back andforth into a guide box through a rigid guide tube and a flexible adaptive tube, connectedto each other. The wire is rigidly attached to a flexible nitinol catheter by means ofkeyed cuff. The angular orientation of the shielded source, which is attached to the otherside of the nitinol catheter, is fixed and known for every dwell position inside eachneedle, through the engagement of proximal keyed cuffs and the keyways cut into theconnector. The overall multisource RSBT system enables controlling the depth positioningas well as the rotations of the shielded sources in a decoupled manner.

Multisource Rotating Shield Brachytherapy Apparatus for Prostate Cancer (4)

2.D. Dose delivery methodology

The delivery process occurs by having the moving template control the angulardirections of all the source/shield combinations and using the remote afterloader toindependently control the longitudinal position of all the sources in all the needlessimultaneously. Once the source angles are changed by translating the moving template, themultisource afterloader moves the sources to all of the necessary depths in each needle.The process is repeated for all of the sixteen evenly-spaced emission directions per dwellposition. This has been found to be sufficient to ensure CTV coverage and urethralsparing, with 5 mm spacing between dwell positions. Thus, in this technique the cathetersare rotated by 22.5°, and only a single 360° catheter rotation is neededfor a full treatment. The designed angular drive apparatus forces the sources to be at thesame angle at the same time while the longitudinal depth of the sources inside needles canbe adjusted in different positions. Therefore the total amount of time spent on a specificemission direction is dictated by the catheter that requires the greatest total dwell timeto deliver.

The shielded source for each needle can be retracted back into the afterloaderwithin less than 10 seconds in the event of an emergency. Each implanted needle has itsown partially-shielded RSBT source, and the radiation from all sources is deliveredsimultaneously. RSBT delivery with this novel multisource apparatus involves inserting theneedles, without catheters, through the perineum under ultrasound guidance. The needleswill be CT/MRI compatible, and sterilizable.

2.E. Treatment planning

In order to assess the dosimetric effectiveness, delivery times, and robustnessto uncertainties of the proposed RSBT approach, comparative treatment plans for RSBT andHDR-BT were generated on computed tomography (CT) images of a previously treated anonymouspatient for whom 19 needles were used. Based on the methods of the CaliforniaEndocurietherapy Institute for treatment planning,³⁸ a 5-mm margin is added to the prostate boundary, excluding theregions adjacent to the bladder, rectum, and the proximal seminal vesicles, in order tocontour the CTV. The urethral margin of 3 mm was included in the model as a relaxedprescription dose constraint in order to provide a spatial location for the dose gradientabout the urethra. The CTV D₉₀ (minimum dose to the hottest90% of the CTV) is set to 110% of the prescribed dose (20 Gy). CTVV₁₀₀ and V₁₅₀ are required to bein the range of 90% to 100% and <35%, respectively.D_0.1cc values for the rectal wall, the bladder wall, and theurethra were limited to less than 85%, 100%, and 110%,respectively. D_1cc values for the same set of organs at riskwere also limited to less than 80%, 90%, and 105%, respectively.The optimization method is the same as that described in a previous study.³¹

2.F. Uncertainty tolerance

A sensitivity analysis was performed in order to estimate the dosimetric impactof uncertainty in both longitudinal positions and emission angles of the shieldedcatheters. A combination of multiple different systematic longitudinal positioning errors(≤ 2 mm) as well as rotational orientation errors (≤ 15°) of theshielded catheters is considered in order to determine the uncertainty tolerance of theRSBT multisource delivery system. CTV D₉₀ and urethraD_0.1cc were evaluated following error application toquantify plan degradation due to uncertainty, with ±3% accuracy consideredtolerable. The assumption is based on the plausible scenario of rotating all of thecatheters the same incorrect angle as well as translating all of the catheters the sameincorrect distance.

3. RESULTS

Planned conventional HDR-BT and RSBT dose distributions as well as dose volumehistograms (DVH) are shown in Figure 5a–b and5c, respectively, for the urethral gradient margin of3 mm. For the same CTV D₉₀ of the patient considered and 3 mmurethral margin, the planned treatment with the multisource RSBT apparatus reduced urethralD_0.1cc below that of ¹⁹²Ir-based HDR-BT by31% relative to the prescribed dose of 100%. Plots of the urethralD_0.1cc and CTV D₉₀ percentagevariations as a function of emission direction rotational error and catheter positionalerror are shown in Figure 6a and 6b, respectively. The urethral dose change relative to zero error iswithin the ±3% tolerance for ±1 mm positioning error and±7° angular errors.

Multisource Rotating Shield Brachytherapy Apparatus for Prostate Cancer (5)

Multisource Rotating Shield Brachytherapy Apparatus for Prostate Cancer (6)

With the increasing values of angular deviation of the source’s emissiondirection from the ideal state of zero degree error, urethralD_0.1cc value increases as shown in Figure 6 (a). The systematic angular error of 15° from thebaseline increased the urethral D_0.1cc by 8%. For thecase considered, urethral D_0.1cc increased by 3% with 2mm positional error. Figure 6 (a) shows that when allof the catheters have 2 mm longitudinal errors and are rotated 15° incorrectly,there is a 11.6% increase in urethral D_0.1cc. Figure 6 (b) shows that the catheters’ emissiondirection error could either increase or decrease the value of CTVD₉₀. For the same urethral dose gradient volume peri-apicalD_0.1cc was reduced by 25%. The delivery time for 20 Gyto the CTV for the case considered was 15.8 min with HDR-BT using a 370 GBq ¹⁹²Irsource and 121.7 min with RSBT.

4. DISCUSSION

A urethral margin of 3 mm was added to the boundary of the urethra for the caseconsidered, irrespective of the prostate size, and no constraints were applied to the doseinside the margin in the treatment planning process. The resulting dose distributionsindicate that RSBT with the proposed multisource apparatus induced cold spots only insideand adjacent to the urethra, which is desirable in terms of minimizing normal tissuetoxicity. Besides that, the DVH plots exhibit a shift to the left in the urethral DVHrelative to that of conventional HDR-BT technique. However the physician would need toselect the appropriate margin for a given patient.

The proposed mechanism in Figure 4 offers anumber of unique attributes. First, the dimensions of the unit are small enough that thesystem can be used in common procedure rooms. Second, as the connectors have the freedom tomove longitudinally prior to the connection between the angular drive mechanism and theneedles, the depth of needles entry into the patient’s perineum does not matter.Third, although the angular drive mechanism dictates all of the 20 emission windows in thepatient to be at the same direction during the irradiation process, the independent depthcontrol for each shielded source enabled by the multisource remote afterloader providesefficient treatments. Fourth, the control over longitudinal translation and the control overrotation of the shielded sources into the needles are independent.

All of the shielded sources’ aluminium emission windows are oriented inthe same emission direction at the same time during the irradiation process. Therefore thedelivery scheme would be based on completing all of the dwell positions of all the cathetersin a single rotational angle and then switching to the next rotational angle by means oftranslating the moving template one sixteenth of the distance needed to create a single fullrotation of the catheters. Accordingly the total amount of time spent on a single emissiondirection is dictated by the catheter with the longest cumulative dwell time for thatdirection. The treatment time for delivering RSBT dose with multisource RSBT apparatus showsan increase by a factor of about 7 relative to the conventional HDR-BT treatment time due tothe lower dose rate of ¹⁵³Gd relative to ¹⁹²Ir. As all of the shieldedsources have the same orientation in a single translational position of the moving template,inter-source attenuation is a potential concern with the proposed approach. Our strategy foraddressing this issue is to develop a delivery optimization approach in which thelongitudinal positions for all of the sources for a given delivery angle are intelligentlyordered in time to minimize inter-source attenuation.

The precision of radiation dose delivery of multisource RSBT apparatus as well assafe delivery of high radiation doses to the prostate should be guaranteed during thetreatment. For the presented mechanism it is dependent on the precise longitudinal androtational positioning of the catheters during the irradiation process in which the catheterangles are simultaneously incremented. Therefore, a catheter position monitoring and controlsystem is needed in order to empirically verify that the catheter angles and depths arewithin the required tolerances for safe radiation delivery. This is accomplished with amechanism using feedback from multiple cameras to measure and correct for catheterlongitudinal and angular positioning errors in real time.

It is expected that RSBT delivery would take place under trans-rectal ultrasound(TRUS) guidance. The current version of the RSBT angular drive mechanism is designed todemonstrate mechanical feasibility of the approach and is not yet compatible with acommercially available TRUS system. It is expected that modifications can be successfullymade to the angular drive mechanism to enable TRUS usage, and the associated workflows canlater be defined.

To the authors’ knowledge, the concept of using a rotating shieldbrachytherapy approach similar to that proposed in the current work to treat prostate cancerdates back to the work of Ebert.³⁷ Ebertidentified the potential of the method but no isotope, shielded catheter design, orpractical method for achieving delivery was presented. The system described by the authorsin a previously published paper and the current manuscript fills those major gaps. Strandedprostate seeds do not contain partial shields, and, once implanted, they cannot be rotatedto the knowledge of the authors. The same holds for iridium ribbons, which have an isotopewith an energy that is too high for partial shielding in an interstitial setting.

As the focus of this study is on presenting a novel apparatus for controllingmultiple shielded radiation sources simultaneously in terms of both depth and angle, only asingle previously treated prostate cancer patient was considered as the case study forcomparing RSBT and ¹⁹²Ir-based HDR-BT, as shown in Figure 5 and described in the Results section. An extensive (> 20patients) treatment planning study comparing RSBT and ¹⁹²Ir-based HDR-BT needs tobe conducted in order to thoroughly evaluate the proposed technique, which is planned asfuture work. As designing a feasible RSBT delivery apparatus was a major undertaking thatneeded to be completed prior to conducting the RSBT versus HDR-BT treatment planning study,the scope of the current work was limited to the delivery apparatus itself and a simpleHDR-BT to RSBT comparison to demonstrate feasibility.

There is inter-patient variation in the urethral dose delivered with HDR-BT, andWhite et al (2012)³⁸ reported a meanurethra D_0.1cc value of 107.3% with a standard deviationof only 3%, over 208 separate implants (104 patients). Based on the presented resultthat urethral D_0.1cc can be reduced by 31% when usingRSBT versus HDR-BT, it is expected that the reduction in urethralD_0.1cc will greatly exceed the inter-patient variability forHDR-BT.

Treatment times for the proposed RSBT system are longer than for conventionalHDR-BT, thus the optimizing the associated clinical workflow will require furtherinvestigation. However, its extended treatment times may be not so long as to make theapproach clinically infeasible. For instance, with conventional HDR-BT using intra-operativeTRUS based treatment planning,^6,39–42 asingle procedure, starting with needle implantation, can be completed within 2–3hours.⁴³ With the proposed system, theprocess would be extended to 4–5 hours.

5. CONCLUSIONS

The proposed multisource RSBT delivery apparatus enables a mechanically feasibleurethra-sparing treatment technique for prostate cancer in a clinically reasonable timeframetwo hours.

A novel multisource rotating shield brachytherapy system is proposed as a mechanicallyfeasible alternative to high dose rate brachytherapy for the treatment of locally-advancedprostate cancer. The design consists of a multisource remote afterloader and an angulardrive mechanism which can simultaneously control depths and angles of multiple partiallyshielded radiation sources, respectively. The resulting apparatus can be used to spare theurethra with minimal compromise of the prostate dose.

Acknowledgments

This study was supported by the National Institute of Health through a grant from theNational Institute of Biomedical Imaging and Bioengineering (R01 EB020665) and a NationalCancer Institute Phase I Small Business Technology Transfer grant (1 R41 CA210737-01).

Footnotes

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Conflict of Interest

RTF has ownership interest in pxAlpha, LLC, which is developing a rotating shieldbrachytherapy delivery method.

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